Prostaglandin E2: From Clinical Applications to Its Potential Role in Bone- Muscle Crosstalk and Myogenic Differentiation
Chenglin Mo, Sandra Romero-Suarez, Lynda Bonewald, Mark Johnson and Marco Brotto
Affiliation: Muscle Biology Research Group-MUBIG, School of Nursing, University of Missouri-Kansas, Health Sciences Building 2246, Kansas City, MO, 64108, USA.
Prostaglandin E2 (PGE2), a prostanoid synthesized from arachidonic acid via the cyclooxygenase pathway, is a
modulator of physiological responses including inflammation, fever, and muscle regeneration. Several patents have been
filed that are related to PGE2, one of them being directly related to skeletal muscles. In this report, we first summarize the
key patents describing inventions for the utilization of PGE2 for either diagnostic or therapeutic purposes, including skeletal
muscle. In the second part of our work we present new and exciting data that demonstrates that PGE2 accelerates skeletal
muscle myogenic differentiation. Our discovery resulted from our recent and novel concept of bone-muscle crosstalk.
Bone and muscle are anatomically intimate endocrine organs and we aimed to determine whether this anatomical intimacy
also translates into a biochemical communication from bone cells to muscle cells at the in vitro level. The effects of MLOY4
osteocyte-like cell conditioned medium (CM) and three osteocyte-secreted factors, PGE2, sclerostin and monocyte
chemotactic protein (MCP-3), on C2C12 myogenic differentiation were evaluated using morphological analyses, a customized
96-gene PCR array, and measurements of intracellular calcium levels. MLO-Y4 CM and PGE2, but not sclerostin
and MCP-3, induced acceleration of myogenesis of C2C12 myoblasts that was linked with significant modifications in intracellular
calcium homeostasis. This finding should further stimulate the pursuit of new patents to explore the use of
PGE2 and the new concept of bone-muscle crosstalk for the development and application of inventions designed to treat
muscle diseases characterized by enhanced muscle wasting, such as sarcopenia.
Keywords: Bone-muscle crosstalk, PGE2, inventions, prostaglandins, prostanoid, EP Receptors, gene expression, MyoD, muscle
regulatory factors, myogenic acceleration, calcium release, excitation-contraction coupling, bone cells, osteocytes, MLO-Y4
osteocytes-like cells, MLO-Y4 conditioned media, bone secreted factors, muscle secreted factors, myokines, calcium-induced
calcium release (CICR), patents
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