Bone Degeneration, Inflammation and Secondary Complications of Arthritis: Potential Targets and their Natural Inhibitors

Author(s): Mahadevappa Hemshekhar, Ram M. Thushara, Somanathapura K. Naveen Kumar, Manoj Paul, Mahalingam S. Sundaram, Kempaiah Kemparaju, Kesturu S. Girish*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 18 , Issue 3 , 2018

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Graphical Abstract:


Arthritis is marked by joint deterioration that affects articular cartilage and subchondral bone. Though cartilage degradation does the major damage during arthritis, subsequent bone degeneration cannot be neglected. Recent progress in arthritis research has identified the clinical importance of bone erosion in destructive arthritis. Studies have showed the key role played by osteoclasts and receptor activator of nuclear factor kappaB ligand (RANKL) signaling in bone erosion. Cathepsins and tartrate resistant acid phosphatase (TRAP) are considered key enzymatic factors contributing to bone erosion. Further, reactive oxygen species (ROS) formed at the ruffled border of osteoclasts also causes bone resorption and matrix degradation. Besides, severe inflammation during arthritis induces bone erosion by aiding in Ca2+ removal and activating osteoclastogenesis. The inflammatory cytokines and ROS influence osteoclast differentiation by regulating osteoclast-lineage cells or by acting on other cells to regulate the expression of RANKL and osteoprotegerin (OPG). The enhanced production of pro-inflammatory cytokines and ROS in arthritis stimulates tissue injury by means of oxidative damage leading to vital organ damage and synovial and circulatory cell apoptosis. Thus, blocking enzymatic and non-enzymatic factors responsible for bone erosion and inflammation is considered a prime strategy in the management of arthritis. In this review we provide an overview of the mechanisms of bone erosion, inflammation and associated oxidative stress/damage during arthritis perpetuation along with shedding light on potential targets. The article also describes the possible natural therapeutic agents that could prevent bone loss and inflammation, and related secondary complications of arthritis.

Keywords: Arthritis, bone erosion, inflammation, oxidative damage, secondary complications, therapeutic targets.

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Article Details

Year: 2018
Published on: 10 January, 2018
Page: [244 - 275]
Pages: 32
DOI: 10.2174/1389557517666170315144233
Price: $65

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