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Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Cartilage Tissue and Therapeutic Strategies for Cartilage Repair

Author(s): Sahar Khajeh, Farzaneh Bozorg-Ghalati, Mina Zare, Ghodratollah Panahi and Vahid Razban*

Volume 21, Issue 1, 2021

Published on: 10 June, 2020

Page: [56 - 72] Pages: 17

DOI: 10.2174/1566524020666200610170646

Price: $65


High incidence of articular cartilage defects is still a major challenge in orthopedic and trauma surgery worldwide. It also has great socioeconomic effects as it is the major cause of disability in industrialized countries. This highlights the essential need for new treatments. Knowledge about the factors that have been implicated in the pathogenesis of cartilage diseases, including changes in the composition and structure of cartilaginous extracellular matrix (ECM), molecular factors and environmental signaling pathways could help the development of innovative therapeutic strategies.

It is consensuses that the success of any technology aiming to repair chondral defects will be dependent upon its ability to produce tissues that most closely replicate the mechanical and biochemical properties of native cartilage. Increasing the knowledge about cartilage tissue and its molecular biomarkers could help find new and useful therapeutic approaches in cartilage damage. This review tries to describe cartilage tissue biology in detail and discuss different available therapeutic modalities with their pros and cons. New cartilage regeneration strategies and therapies, focusing on cellbased therapy and tissue engineering, and their underlying molecular and cellular bases will be pointed out as well.

Keywords: Articular cartilage, stem cell therapy, autologous chondrocyte implantation, tissue engineering.

Cohen NP, Foster RJ, Mow VC. Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state. J Orthop Sports Phys Ther 1998; 28(4): 203-15.
[] [PMID: 9785256]
Mobasheri A, Kalamegam G, Musumeci G, Batt ME. Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions. Maturitas 2014; 78(3): 188-98.
[] [PMID: 24855933]
Chen S, Fu P, Cong R, Wu H, Pei M. Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis 2015; 2(1): 76-95.
[] [PMID: 26000333]
Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol 2007; 213(3): 626-34.
[] [PMID: 17786965]
Behonick DJ, Werb Z. A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte. Mech Dev 2003; 120(11): 1327-36.
[] [PMID: 14623441]
Muir H. The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules. BioEssays 1995; 17(12): 1039-48.
[] [PMID: 8634065]
Kučera L. Biological properties of the hyaluronan-tyramine hydrogel for cartilage tissue replacement. Faculty of Science, Masaryk University Department of Experimental Biology 2014; p. 142.
Archer CW, Francis-West P. The chondrocyte. Int J Biochem Cell Biol 2003; 35(4): 401-4.
[] [PMID: 12565700]
Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 1998; 47: 487-504.
[PMID: 9571450]
Bora FW Jr, Miller G. Joint physiology, cartilage metabolism, and the etiology of osteoarthritis. Hand Clin 1987; 3(3): 325-36.
[PMID: 3308909]
Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect 1998; 47: 477-86..
[PMID: 9571449]
Millward-Sadler SJ, Salter DM. Integrin-dependent signal cascades in chondrocyte mechanotransduction. Ann Biomed Eng 2004; 32(3): 435-46.
[] [PMID: 15095818]
Khajeh S, et al. Enhanced chondrogenic differentiation of dental pulp-derived mesenchymal stem cells in 3D pellet culture system: effect of mimicking hypoxia. Biologia 2018; 73(7): 715-26.
Mobasheri A, Carter SD, Martín-Vasallo P, Shakibaei M. Integrins and stretch activated ion channels; putative components of functional cell surface mechanoreceptors in articular chondrocytes. Cell Biol Int 2002; 26(1): 1-18.
[] [PMID: 11779216]
Allison DD, Grande-Allen KJ. Review. Hyaluronan: a powerful tissue engineering tool. Tissue Eng 2006; 12(8): 2131-40.
[] [PMID: 16968154]
Cohen M, Klein E, Geiger B, Addadi L. Organization and adhesive properties of the hyaluronan pericellular coat of chondrocytes and epithelial cells. Biophys J 2003; 85(3): 1996-2005.
[] [PMID: 12944312]
Bastow ER, Byers S, Golub SB, Clarkin CE, Pitsillides AA, Fosang AJ. Hyaluronan synthesis and degradation in cartilage and bone. Cell Mol Life Sci 2008; 65(3): 395-413.
[] [PMID: 17965830]
Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 2004; 4(7): 528-39.
[] [PMID: 15229478]
Locci P, Marinucci L, Lilli C, Martinese D, Becchetti E. Transforming growth factor beta 1-hyaluronic acid interaction. Cell Tissue Res 1995; 281(2): 317-24.
[] [PMID: 7648625]
Meran S, Thomas D, Stephens P, et al. Involvement of hyaluronan in regulation of fibroblast phenotype. J Biol Chem 2007; 282(35): 25687-97.
[] [PMID: 17611197]
Ito T, Williams JD, Fraser D, Phillips AO. Hyaluronan attenuates transforming growth factor-beta1-mediated signaling in renal proximal tubular epithelial cells. Am J Pathol 2004; 164(6): 1979-88.
[] [PMID: 15161634]
Bourguignon LY, Singleton PA, Zhu H, Zhou B. Hyaluronan promotes signaling interaction between CD44 and the transforming growth factor beta receptor I in metastatic breast tumor cells. J Biol Chem 2002; 277(42): 39703-12.
[] [PMID: 12145287]
Brandt KD. Osteoarthritis. Preface. Rheum Dis Clin North Am 2003; 29(4): ix-xiii.
[] [PMID: 14603575]
Eyre D. Collagen of articular cartilage. Arthritis Res 2002; 4(1): 30-5.
[] [PMID: 11879535]
Bhosale AM, Richardson JB. Articular cartilage: structure, injuries and review of management. Br Med Bull 2008; 87: 77-95.
[] [PMID: 18676397]
Aigner T, Stöve J. Collagens--major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. Adv Drug Deliv Rev 2003; 55(12): 1569-93.
[] [PMID: 14623402]
Eyre DR. Collagens and cartilage matrix homeostasis Clin Orthop Relat Res 2004; (427): (Suppl.)S118-22..
[] [PMID: 15480053]
Athanasiou KA, Darling EM, Hu JC. Articular cartilage tissue engineering. Synthesis Lectures on Tissue Engineering 2009; 1(1): 1-182.
[PMID: 20201770]
Zhu M, Feng Q, Bian L. Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels. Acta Biomater 2014; 10(3): 1333-40.
[] [PMID: 24342044]
Lee HH, Chang CC, Shieh MJ, et al. Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect. Sci Rep 2013; 3: 2683.
[] [PMID: 24042188]
Studer D, Millan C, Öztürk E, Maniura-Weber K, Zenobi-Wong M. Molecular and biophysical mechanisms regulating hypertrophic differentiation in chondrocytes and mesenchymal stem cells. Eur Cell Mater 2012; 24(24): 118-35.
[] [PMID: 22828990]
Miao D, Scutt A. Histochemical localization of alkaline phosphatase activity in decalcified bone and cartilage. J Histochem Cytochem 2002; 50(3): 333-40.
[] [PMID: 11850436]
Anderson HC. Matrix vesicles and calcification. Curr Rheumatol Rep 2003; 5(3): 222-6.
[] [PMID: 12744815]
Balcerzak M, Hamade E, Zhang L, et al. The roles of annexins and alkaline phosphatase in mineralization process. Acta Biochim Pol 2003; 50(4): 1019-38.
[] [PMID: 14739992]
Sun MM, Beier F. Chondrocyte hypertrophy in skeletal development, growth, and disease. Birth Defects Res C Embryo Today 2014; 102(1): 74-82.
[] [PMID: 24677724]
Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res 2005; 8(1): 11-7.
[] [PMID: 15667640]
Böhme K, Conscience-Egli M, Tschan T, Winterhalter KH, Bruckner P. Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine. J Cell Biol 1992; 116(4): 1035-42.
[] [PMID: 1734018]
DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage 2000; 8(5): 309-34.
[] [PMID: 10966838]
Kronenberg HM. Developmental regulation of the growth plate. Nature 2003; 423(6937): 332-6.
[] [PMID: 12748651]
Sandell LJ, Sugai JV, Trippel SB. Expression of collagens I, II, X, and XI and aggrecan mRNAs by bovine growth plate chondrocytes in situ. J Orthop Res 1994; 12(1): 1-14.
[] [PMID: 8113931]
Kirsch T, Nah HD, Shapiro IM, Pacifici M. Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes. J Cell Biol 1997; 137(5): 1149-60.
[] [PMID: 9166414]
Heymer A. Chondrogenic Differentiation of Human Mesenchymal Stem Cells and Articular Cartilage Reconstruction. Würzburg 2008; p. 122.
Nöth U, Rackwitz L, Heymer A, et al. Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels. J Biomed Mater Res A 2007; 83(3): 626-35.
[] [PMID: 17503531]
Zhong L, Huang X, Karperien M, Post JN. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes. Int J Mol Sci 2015; 16(8): 19225-47.
[] [PMID: 26287176]
Mahmoudifar N, Doran PM. Chondrogenesis and cartilage tissue engineering: the longer road to technology development. Trends Biotechnol 2012; 30(3): 166-76.
[] [PMID: 22071143]
Shang J, Liu H, Li J, Zhou Y. Roles of hypoxia during the chondrogenic differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther 2014; 9(2): 141-7.
[] [PMID: 24372326]
Ahmed TA, Hincke MT. Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev 2010; 16(3): 305-29.
[] [PMID: 20025455]
Mamidi MK, Das AK, Zakaria Z, Bhonde R. Mesenchymal stromal cells for cartilage repair in osteoarthritis. Osteoarthritis Cartilage 2016; 24(8): 1307-16.
[] [PMID: 26973328]
Mobasheri A, et al. Facilitative glucose transporters in articular chondrocytes. Expression, distribution and functional regulation of GLUT isoforms by hypoxia, hypoxia mimetics, growth factors and pro-inflammatory cytokines. Adv Anat Embryol Cell Biol 2008; 200: 1-84.
Goggs R, Carter SD, Schulze-Tanzil G, Shakibaei M, Mobasheri A. Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. Vet J 2003; 166(2): 140-58.
[] [PMID: 12902179]
Ouzzine M, Venkatesan N, Fournel-Gigleux S. Proteoglycans and cartilage repair. Methods Mol Biol 2012; 836: 339-55.
[] [PMID: 22252645]
Duan L, Liang Y, Ma B, Zhu W, Wang D. Epigenetic regulation in chondrocyte phenotype maintenance for cell-based cartilage repair. Am J Transl Res 2015; 7(11): 2127-40.
[PMID: 26807163]
Falah M, Nierenberg G, Soudry M, Hayden M, Volpin G. Treatment of articular cartilage lesions of the knee. Int Orthop 2010; 34(5): 621-30.
[] [PMID: 20162416]
Solursh M. Formation of cartilage tissue in vitro. J Cell Biochem 1991; 45(3): 258-60.
[] [PMID: 2066375]
Wang M, Yuan Z, Ma N, et al. Advances and Prospects in Stem Cells for Cartilage Regeneration. Stem Cells Int 2017.20174130607
[] [PMID: 28246531]
Wang L, et al. Adult Stem Cells and Hydrogels for Cartilage Regeneration. Curr Stem Cell Res Ther 2017.
[PMID: 28494722]
McKee C, Hong Y, Yao D, Chaudhry GR. Compression Induced Chondrogenic Differentiation of Embryonic Stem Cells in Three-Dimensional Polydimethylsiloxane Scaffolds. Tissue Eng Part A 2017; 23(9-10): 426-35.
[] [PMID: 28103756]
Martín AR, Patel JM, Zlotnick HM, Carey JL, Mauck RL. Emerging therapies for cartilage regeneration in currently excluded ‘red knee’ populations. NPJ Regen Med 2019; 4: 12.
[] [PMID: 31231546]
Zhang L, Hu J, Athanasiou KA. The role of tissue engineering in articular cartilage repair and regeneration. Crit Rev Biomed Eng 2009; 37(1-2): 1-57.
[] [PMID: 20201770]
Camp CL, Stuart MJ, Krych AJ. Current concepts of articular cartilage restoration techniques in the knee. Sports Health 2014; 6(3): 265-73.
[] [PMID: 24790697]
Puelacher WC, Kim SW, Vacanti JP, Schloo B, Mooney D, Vacanti CA. Tissue-engineered growth of cartilage: the effect of varying the concentration of chondrocytes seeded onto synthetic polymer matrices. Int J Oral Maxillofac Surg 1994; 23(1): 49-53.
[] [PMID: 8163862]
Hubka KM, Dahlin RL, Meretoja VV, Kasper FK, Mikos AG. Enhancing chondrogenic phenotype for cartilage tissue engineering: monoculture and coculture of articular chondrocytes and mesenchymal stem cells. Tissue Eng Part B Rev 2014; 20(6): 641-54.
[] [PMID: 24834484]
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331(14): 889-95.
[] [PMID: 8078550]
Poussa M, Rubak J, Ritsilä V. Differentiation of the osteochondrogenic cells of the periosteum in chondrotrophic environment. Acta Orthop Scand 1981; 52(3): 235-9.
[] [PMID: 7282318]
Rubak JM, Poussa M, Ritsilä V. Effects of joint motion on the repair of articular cartilage with free periosteal grafts. Acta Orthop Scand 1982; 53(2): 187-91.
[] [PMID: 6753459]
Rubak JM, Poussa M, Ritsilä V. Chondrogenesis in repair of articular cartilage defects by free periosteal grafts in rabbits. Acta Orthop Scand 1982; 53(2): 181-6.
[] [PMID: 6753458]
Niedermann B, Boe S, Lauritzen J, Rubak JM. Glued periosteal grafts in the knee. Acta Orthop Scand 1985; 56(6): 457-60.
[] [PMID: 3879088]
Rubak JM. Reconstruction of articular cartilage defects with free periosteal grafts. An experimental study. Acta Orthop Scand 1982; 53(2): 175-80.
[] [PMID: 6753457]
Grande DA, Singh IJ, Pugh J. Healing of experimentally produced lesions in articular cartilage following chondrocyte transplantation. Anat Rec 1987; 218(2): 142-8.
[] [PMID: 3619082]
Smith GD, Knutsen G, Richardson JB. A clinical review of cartilage repair techniques. J Bone Joint Surg Br 2005; 87(4): 445-9.
[] [PMID: 15795189]
Xiang Y, Bunpetch V, Zhou W, Ouyang H. Optimization strategies for ACI: A step-chronicle review. J Orthop Translat 2019; 17: 3-14.
[] [PMID: 31194027]
Peterson L, Minas T, Brittberg M, Lindahl A. Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. J Bone Joint Surg Am 2003; 85-A(Suppl. 2): 17-24.
[] [PMID: 12721341]
Brittberg M. Autologous chondrocyte implantation--technique and long-term follow-up. Injury 2008; 39(Suppl. 1): S40-9.
[] [PMID: 18313471]
Peterson L, Brittberg M, Kiviranta I, Akerlund EL, Lindahl A. Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am J Sports Med 2002; 30(1): 2-12.
[] [PMID: 11798989]
Beck JJ, Sugimoto D, Micheli L. Sustained Results in Long-Term Follow-Up of Autologous Chondrocyte Implantation (ACI) for Distal Femur Juvenile Osteochondritis Dissecans (JOCD). Adv Orthop 2018.20187912975
[] [PMID: 30345118]
Berruto M, Ferrua P, Pasqualotto S, et al. Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: A single-centre prospective study. Injury 2017; 48(10): 2230-4.
[] [PMID: 28803652]
Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 2010; 38(6): 1117-24.
[] [PMID: 20181804]
Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation--a systematic review. Osteoarthritis Cartilage 2011; 19(7): 779-91.
[] [PMID: 21333744]
Niemeyer P, Pestka JM, Kreuz PC, et al. Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med 2008; 36(11): 2091-9.
[] [PMID: 18801942]
Lee CR, Grodzinsky AJ, Hsu HP, Martin SD, Spector M. Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee. J Orthop Res 2000; 18(5): 790-9.
[] [PMID: 11117302]
Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000; (374): 212-34.
[] [PMID: 10818982]
Dell’Accio F, De Bari C, Luyten FP. Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum 2001; 44(7): 1608-19.
[<1608:AID-ART284>3.0.CO;2-T] [PMID: 11465712]
Cournil-Henrionnet C, Huselstein C, Wang Y, et al. Phenotypic analysis of cell surface markers and gene expression of human mesenchymal stem cells and chondrocytes during monolayer expansion. Biorheology 2008; 45(3-4): 513-26.
[] [PMID: 18836250]
Jin GZ, Kim HW. Efficacy of collagen and alginate hydrogels for the prevention of rat chondrocyte dedifferentiation. J Tissue Eng 2018.92041731418802438
[] [PMID: 30305887]
Wuest SL, Caliò M, Wernas T, et al. Influence of Mechanical Unloading on Articular Chondrocyte Dedifferentiation. Int J Mol Sci 2018; 19(5)E1289
[] [PMID: 29693628]
Duan L, Liang Y, Ma B, et al. DNA Methylation Profiling in Chondrocyte Dedifferentiation In Vitro. J Cell Physiol 2017; 232(7): 1708-16.
[] [PMID: 27404036]
Williams R, Khan IM, Richardson K, et al. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One 2010; 5(10)e13246
[] [PMID: 20976230]
Newman AP. Articular cartilage repair. Am J Sports Med 1998; 26(2): 309-24.
[] [PMID: 9548130]
Langer R, Vacanti JP. Tissue engineering. Science 1993; 260(5110): 920-6.
[] [PMID: 8493529]
Siminovitch L, McCulloch EA, Till JE. The Distribution of Colony-Forming Cells among Spleen Colonies. J Cell Comp Physiol 1963; 62: 327-36.
[] [PMID: 14086156]
Jones EA, English A, Henshaw K, et al. Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum 2004; 50(3): 817-27.
[] [PMID: 15022324]
Young HE, Steele TA, Bray RA, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 2001; 264(1): 51-62.
[] [PMID: 11505371]
De Bari C, Dell’Accio F, Vanlauwe J, et al. Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. Arthritis Rheum 2006; 54(4): 1209-21.
[] [PMID: 16575900]
Trubiani O, Di Primio R, Traini T, et al. Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int J Immunopathol Pharmacol 2005; 18(2): 213-21.
[] [PMID: 15888245]
Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006; 99(5): 1285-97.
[] [PMID: 16795045]
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24(5): 1294-301.
[] [PMID: 16410387]
Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci 2000; 113(Pt 1): 5-10.
[PMID: 10591620]
Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282(5391): 1145-7.
[] [PMID: 9804556]
Kramer J, Hegert C, Guan K, Wobus AM, Müller PK, Rohwedel J. Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech Dev 2000; 92(2): 193-205.
[] [PMID: 10727858]
Zhang L, Su P, Xu C, Yang J, Yu W, Huang D. Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol Lett 2010; 32(9): 1339-46.
[] [PMID: 20464452]
Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM. 2010 Nicolas Andry Award: Multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop Relat Res 2010; 468(9): 2530-40.
[] [PMID: 20625952]
Barry FP. Mesenchymal stem cell therapy in joint disease. Novartis Found Symp 2003; 249: 86-96.
Razban V, et al. Tube formation potential of BMSCs and USSCs in response to HIF-1α overexpression under hypoxia. Cytol Genet 2018; 52(3): 236-44.
Razban V, et al. Engineered Heparan Sulfate-Collagen IV Surfaces Improve Human Mesenchymal Stem Cells Differentiation to Functional Hepatocyte-Like Cells. J Biomater Tissue Eng 2014; 4(10): 811-22.
Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 2007; 213(2): 341-7.
[] [PMID: 17620285]
Chang YJ, Shih DT, Tseng CP, Hsieh TB, Lee DC, Hwang SM. Disparate mesenchyme-lineage tendencies in mesenchymal stem cells from human bone marrow and umbilical cord blood. Stem Cells 2006; 24(3): 679-85.
[] [PMID: 16179428]
Panepucci RA, Siufi JL, Silva WA Jr, et al. Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 2004; 22(7): 1263-78.
[] [PMID: 15579645]
Lei J, Hui D, Huang W, et al. Heterogeneity of the biological properties and gene expression profiles of murine bone marrow stromal cells. Int J Biochem Cell Biol 2013; 45(11): 2431-43.
[] [PMID: 23911306]
Richardson SM, Kalamegam G, Pushparaj PN, et al. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 2016; 99: 69-80.
[] [PMID: 26384579]
Somoza RA, Welter JF, Correa D, Caplan AI. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng Part B Rev 2014; 20(6): 596-608.
[] [PMID: 24749845]
Chen X, Zhang F, He X, et al. Chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells in type I collagen-hydrogel for cartilage engineering. Injury 2013; 44(4): 540-9.
[] [PMID: 23337703]
Wang L, Seshareddy K, Weiss ML, Detamore MS. Effect of initial seeding density on human umbilical cord mesenchymal stromal cells for fibrocartilage tissue engineering. Tissue Eng Part A 2009; 15(5): 1009-17.
[] [PMID: 18759671]
Nirmal RS, Nair PD. Significance of soluble growth factors in the chondrogenic response of human umbilical cord matrix stem cells in a porous three dimensional scaffold. Eur Cell Mater 2013; 26: 234-51.
[] [PMID: 24213879]
Reppel L, Schiavi J, Charif N, et al. Chondrogenic induction of mesenchymal stromal/stem cells from Wharton’s jelly embedded in alginate hydrogel and without added growth factor: an alternative stem cell source for cartilage tissue engineering. Stem Cell Res Ther 2015; 6: 260.
[] [PMID: 26718750]
Bian L, Zhai DY, Zhang EC, Mauck RL, Burdick JA. Dynamic compressive loading enhances cartilage matrix synthesis and distribution and suppresses hypertrophy in hMSC-laden hyaluronic acid hydrogels. Tissue Eng Part A 2012; 18(7-8): 715-24.
[] [PMID: 21988555]
Bian L, Zhai DY, Mauck RL, Burdick JA. Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage. Tissue Eng Part A 2011; 17(7-8): 1137-45.
[] [PMID: 21142648]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[] [PMID: 10102814]
Zaim M, Karaman S, Cetin G, Isik S. Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Ann Hematol 2012; 91(8): 1175-86.
[] [PMID: 22395436]
Caplan AI, Elyaderani M, Mochizuki Y, Wakitani S, Goldberg VM. Principles of cartilage repair and regeneration. Clin Orthop Relat Res 1997; (342): 254-69.
[] [PMID: 9308548]
Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 1998; 238(1): 265-72.
[] [PMID: 9457080]
Wu YN, Yang Z, Hui JH, Ouyang HW, Lee EH. Cartilaginous ECM component-modification of the micro-bead culture system for chondrogenic differentiation of mesenchymal stem cells. Biomaterials 2007; 28(28): 4056-67.
[] [PMID: 17590431]
Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276(5309): 71-4.
[] [PMID: 9082988]
Barry FP, Murphy JM, English K, Mahon BP. Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft. Stem Cells Dev 2005; 14(3): 252-65.
[] [PMID: 15969620]
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72.
[] [PMID: 18035408]
Boreström C, Simonsson S, Enochson L, et al. Footprint-free human induced pluripotent stem cells from articular cartilage with redifferentiation capacity: a first step toward a clinical-grade cell source. Stem Cells Transl Med 2014; 3(4): 433-47.
[] [PMID: 24604283]
Hu K. All roads lead to induced pluripotent stem cells: the technologies of iPSC generation. Stem Cells Dev 2014; 23(12): 1285-300.
[] [PMID: 24524728]
Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, Tsumaki N. Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors. PLoS One 2013; 8(10)e77365
[] [PMID: 24146984]
Lewis EB. A gene complex controlling segmentation in Drosophila. Nature 1978; 276(5688): 565-70.
[] [PMID: 103000]
Wellik DM. Hox patterning of the vertebrate axial skeleton. Dev Dyn 2007; 236(9): 2454-63.
[] [PMID: 17685480]
Rinn JL, Bondre C, Gladstone HB, Brown PO, Chang HY. Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet 2006; 2(7)e119
[] [PMID: 16895450]
Ackema KB, Charité J. Mesenchymal stem cells from different organs are characterized by distinct topographic Hox codes. Stem Cells Dev 2008; 17(5): 979-91.
[] [PMID: 18533811]
Leucht P, Kim JB, Amasha R, James AW, Girod S, Helms JA. Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration. Development 2008; 135(17): 2845-54.
[] [PMID: 18653558]
Myers P. Hox genes in development: The Hox code. Nature Education 2008; 1(1): 2.
Barber BA, Rastegar M. Epigenetic control of Hox genes during neurogenesis, development, and disease. Ann Anat 2010; 192(5): 261-74.
[] [PMID: 20739155]
Seifert A, Werheid DF, Knapp SM, Tobiasch E. Role of Hox genes in stem cell differentiation. World J Stem Cells 2015; 7(3): 583-95.
[] [PMID: 25914765]
Liedtke S, Freytag EM, Bosch J, et al. Neonatal mesenchymal-like cells adapt to surrounding cells. Stem Cell Res (Amst) 2013; 11(1): 634-46.
[] [PMID: 23660338]
Dvořáková J, Kučera L, Kučera J, et al. Chondrogenic differentiation of mesenchymal stem cells in a hydrogel system based on an enzymatically crosslinked tyramine derivative of hyaluronan. J Biomed Mater Res A 2014; 102(10): 3523-30.
[] [PMID: 24243864]
Djouad F, Delorme B, Maurice M, et al. Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes. Arthritis Res Ther 2007; 9(2): R33.
[] [PMID: 17391539]
Leyh M, Seitz A, Dürselen L, et al. Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes. Arthritis Res Ther 2014; 16(5): 453.
[] [PMID: 25296561]
Byers BA, Mauck RL, Chiang IE, Tuan RS. Transient exposure to transforming growth factor beta 3 under serum-free conditions enhances the biomechanical and biochemical maturation of tissue-engineered cartilage. Tissue Eng Part A 2008; 14(11): 1821-34.
[] [PMID: 18611145]
Lima EG, Bian L, Ng KW, et al. The beneficial effect of delayed compressive loading on tissue-engineered cartilage constructs cultured with TGF-beta3. Osteoarthritis Cartilage 2007; 15(9): 1025-33.
[] [PMID: 17498976]
Huang AH. Enhancing mesenchymal stem cell chondrogenesis for cartilage tissue engineering University of Pennsylvania, Part of the Molecular, Cellular, and Tissue Engineering Commons. 2010.
Fan L, Chen J, Tao Y, et al. Enhancement of the chondrogenic differentiation of mesenchymal stem cells and cartilage repair by ghrelin. J Orthop Res 2019; 37(6): 1387-97.
[] [PMID: 30644571]
Böhme K, Winterhalter KH, Bruckner P. Terminal differentiation of chondrocytes in culture is a spontaneous process and is arrested by transforming growth factor-β 2 and basic fibroblast growth factor in synergy. Exp Cell Res 1995; 216(1): 191-8.
[] [PMID: 7813620]
Jikko A, Kato Y, Hiranuma H, Fuchihata H. Inhibition of chondrocyte terminal differentiation and matrix calcification by soluble factors released by articular chondrocytes. Calcif Tissue Int 1999; 65(4): 276-9.
[] [PMID: 10485977]
Ahmed N, Dreier R, Göpferich A, Grifka J, Grässel S. Soluble signalling factors derived from differentiated cartilage tissue affect chondrogenic differentiation of rat adult marrow stromal cells. Cell Physiol Biochem 2007; 20(5): 665-78.
[] [PMID: 17762193]
Lettry V, Hosoya K, Takagi S, Okumura M. Coculture of equine mesenchymal stem cells and mature equine articular chondrocytes results in improved chondrogenic differentiation of the stem cells. Jpn J Vet Res 2010; 58(1): 5-15.
[PMID: 20645581]
Fischer J, Dickhut A, Rickert M, Richter W. Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis. Arthritis Rheum 2010; 62(9): 2696-706.
[] [PMID: 20496422]
van Beuningen HM, Glansbeek HL, van der Kraan PM, van den Berg WB. Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage 1998; 6(5): 306-17.
[] [PMID: 10197165]
Shen B, Wei A, Whittaker S, et al. The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro. J Cell Biochem 2010; 109(2): 406-16.
[PMID: 19950204]
Shen B, Wei A, Tao H, Diwan AD, Ma DD. BMP-2 enhances TGF-beta3-mediated chondrogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in alginate bead culture. Tissue Eng Part A 2009; 15(6): 1311-20.
[] [PMID: 18950289]
Hui TY, Cheung KM, Cheung WL, Chan D, Chan BP. In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration. Biomaterials 2008; 29(22): 3201-12.
[] [PMID: 18462789]
Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 2005; 23(1): 47-55.
[] [PMID: 15637621]
Lee HJ, Yu C, Chansakul T, et al. Enhanced chondrogenesis of mesenchymal stem cells in collagen mimetic peptide-mediated microenvironment. Tissue Eng Part A 2008; 14(11): 1843-51.
[] [PMID: 18826339]
Schagemann JC, Mrosek EH, Landers R, Kurz H, Erggelet C. Morphology and function of ovine articular cartilage chondrocytes in 3-d hydrogel culture. Cells Tissues Organs (Print) 2006; 182(2): 89-97.
[] [PMID: 16804299]
Francioli SE, Candrian C, Martin K, Heberer M, Martin I, Barbero A. Effect of three-dimensional expansion and cell seeding density on the cartilage-forming capacity of human articular chondrocytes in type II collagen sponges. J Biomed Mater Res A 2010; 95(3): 924-31.
[] [PMID: 20845491]
George J, Kuboki Y, Miyata T. Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds. Biotechnol Bioeng 2006; 95(3): 404-11.
[] [PMID: 16572435]
Brochhausen C, Sánchez N, Halstenberg S, et al. Phenotypic redifferentiation and cell cluster formation of cultured human articular chondrocytes in a three-dimensional oriented gelatin scaffold in the presence of PGE2--first results of a pilot study. J Biomed Mater Res A 2013; 101(8): 2374-82.
[] [PMID: 23377957]
Williams CG, Kim TK, Taboas A, Malik A, Manson P, Elisseeff J. In vitro chondrogenesis of bone marrow-derived mesenchymal stem cells in a photopolymerizing hydrogel. Tissue Eng 2003; 9(4): 679-88.
[] [PMID: 13678446]
Dickhut A, Gottwald E, Steck E, Heisel C, Richter W. Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo. Front Biosci 2008; 13: 4517-28.
[] [PMID: 18508526]
Kurkalli BG, Gurevitch O, Sosnik A, Cohn D, Slavin S. Repair of bone defect using bone marrow cells and demineralized bone matrix supplemented with polymeric materials. Curr Stem Cell Res Ther 2010; 5(1): 49-56.
[] [PMID: 19807659]
Gurevitch O, Kurkalli BG, Prigozhina T, Kasir J, Gaft A, Slavin S. Reconstruction of cartilage, bone, and hematopoietic microenvironment with demineralized bone matrix and bone marrow cells. Stem Cells 2003; 21(5): 588-97.
[] [PMID: 12968113]
Leyh M. Microenvironment of osteoarthritic cartilage and subchondral bone influences chondrogenic differentiation, extracellular matrix production and composition of bone marrow-derived stem cells and articular chondrocytes. Faculty of Biology of the University Regensburg 2015; p. 130.
Ho ST, Cool SM, Hui JH, Hutmacher DW. The influence of fibrin based hydrogels on the chondrogenic differentiation of human bone marrow stromal cells. Biomaterials 2010; 31(1): 38-47.
[] [PMID: 19800683]
Lynch B, et al. The effect of hypoxia on thermosensitive poly(N-vinylcaprolactam) hydrogels with tunable mechanical integrity for cartilage tissue engineering. J Biomed Mater Res B Appl Biomater 2016.
[PMID: 27240310 ]
Kanichai M, Ferguson D, Prendergast PJ, Campbell VA. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1alpha. J Cell Physiol 2008; 216(3): 708-15.
[] [PMID: 18366089]
Butler DL, Goldstein SA, Guilak F. Functional tissue engineering: the role of biomechanics. J Biomech Eng 2000; 122(6): 570-5.
[] [PMID: 11192376]
Provot S, Zinyk D, Gunes Y, et al. Hif-1alpha regulates differentiation of limb bud mesenchyme and joint development. J Cell Biol 2007; 177(3): 451-64.
[] [PMID: 17470636]
Thoms BL, Dudek KA, Lafont JE, Murphy CL. Hypoxia promotes the production and inhibits the destruction of human articular cartilage. Arthritis Rheum 2013; 65(5): 1302-12.
[] [PMID: 23334958]
Ollitrault D, Legendre F, Drougard C, et al. BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes. Tissue Eng Part C Methods 2015; 21(2): 133-47.
[] [PMID: 24957638]
Shi Y, Ma J, Zhang X, Li H, Jiang L, Qin J. Hypoxia combined with spheroid culture improves cartilage specific function in chondrocytes. Integr Biol 2015; 7(3): 289-97.
[] [PMID: 25614382]
Ummarino D. Osteoarthritis: Hypoxia protects against cartilage loss by regulating Wnt signalling. Nat Rev Rheumatol 2016; 12(6): 315.
[] [PMID: 27170507]
Henrionnet C, Liang G, Roeder E, et al. * Hypoxia for Mesenchymal Stem Cell Expansion and Differentiation: The Best Way for Enhancing TGFß-Induced Chondrogenesis and Preventing Calcifications in Alginate Beads. Tissue Eng Part A 2017; 23(17-18): 913-22.
[] [PMID: 28385113]
Patel SA, Simon MC. Biology of hypoxia-inducible factor-2alpha in development and disease. Cell Death Differ 2008; 15(4): 628-34.
[] [PMID: 18259197]
Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood 1993; 82(12): 3610-5.
[] [PMID: 8260699]
Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 2006; 70(5): 1469-80.
[] [PMID: 16887934]
Yoo HI, Moon YH, Kim MS. Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells. Korean J Physiol Pharmacol 2016; 20(1): 53-62.
[] [PMID: 26807023]
Maxwell P, Salnikow K. HIF-1: an oxygen and metal responsive transcription factor. Cancer Biol Ther 2004; 3(1): 29-35.
[] [PMID: 14726713]
Badr GA, Zhang JZ, Tang J, Kern TS, Ismail-Beigi F. Glut1 and glut3 expression, but not capillary density, is increased by cobalt chloride in rat cerebrum and retina. Brain Res Mol Brain Res 1999; 64(1): 24-33.
[] [PMID: 9889305]
Pavan M, Galesso D, Secchieri C, Guarise C. Hyaluronic acid alkyl derivative: A novel inhibitor of metalloproteases and hyaluronidases. Int J Biol Macromol 2016; 84: 221-6.
[] [PMID: 26709144]
Pluda S, Pavan M, Galesso D, Guarise C. Hyaluronic acid auto-crosslinked polymer (ACP): Reaction monitoring, process investigation and hyaluronidase stability. Carbohydr Res 2016; 433: 47-53.
[] [PMID: 27442913]
Beninatto R, Barbera C, De Lucchi O, et al. Photocrosslinked hydrogels from coumarin derivatives of hyaluronic acid for tissue engineering applications. Mater Sci Eng C 2019; 96: 625-34.
[] [PMID: 30606574]
Jay GD, Torres JR, Warman ML, Laderer MC, Breuer KS. The role of lubricin in the mechanical behavior of synovial fluid. Proc Natl Acad Sci USA 2007; 104(15): 6194-9.
[] [PMID: 17404241]
Campo GM, Avenoso A, Campo S, D’Ascola A, Nastasi G, Calatroni A. Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes. Biochem Pharmacol 2010; 80(4): 480-90.
[] [PMID: 20435021]
Yoshida H, Nagaoka A, Kusaka-Kikushima A, et al. KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization. Proc Natl Acad Sci USA 2013; 110(14): 5612-7.
[] [PMID: 23509262]
Goldring MB. Articular cartilage degradation in osteoarthritis. HSS J 2012; 8(1): 7-9.
[] [PMID: 23372517]
Little CB, Barai A, Burkhardt D, et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009; 60(12): 3723-33.
[] [PMID: 19950295]
Yoshida M, Sai S, Marumo K, et al. Expression analysis of three isoforms of hyaluronan synthase and hyaluronidase in the synovium of knees in osteoarthritis and rheumatoid arthritis by quantitative real-time reverse transcriptase polymerase chain reaction. Arthritis Res Ther 2004; 6(6): R514-20.
[] [PMID: 15535829]
Girish KS, Kemparaju K, Nagaraju S, Vishwanath BS. Hyaluronidase inhibitors: a biological and therapeutic perspective. Curr Med Chem 2009; 16(18): 2261-88.
[] [PMID: 19519390]
Choi SI, Park SR, Heo TR. Matrix degradation inhibitory effect of Schisandra fructus on human articular cartilage and chondrocytes. J Ethnopharmacol 2006; 106(2): 279-84.
[] [PMID: 16580800]
Sumantran VN, Kulkarni A, Chandwaskar R, et al. Chondroprotective potential of fruit extracts of Phyllanthus emblica in osteoarthritis. Evid Based Complement Alternat Med 2008; 5(3): 329-35.
[] [PMID: 18830448]
Estakhri F, Panjehshahin MR, Tanideh N, et al. The effect of kaempferol and apigenin on allogenic synovial membrane-derived stem cells therapy in knee osteoarthritic male rats Knee 2020.S0968-0160(20)30068-5.
[] [PMID: 32336589]

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