Skeletal Muscles Maintain Osteocyte Viability

Abstract

Osteocyte viability is important to maintain normal bone mass as apoptosis of these cells is a triggering event in the development of osteoporosis. As sarcopenia and osteoporosis often occur concurrently, we hypothesized that skeletal muscles potentially secrete factors that may protect osteocytes from apoptosis. To test this hypothesis, we treated MLO-Y4 osteocyte-like cells with conditioned media (CM) from C2C12 myoblasts or myotubes, and primary muscles. Our results demonstrate that dexamethasone-induced apoptosis of MLO-Y4 osteocyte-like cells is blocked by C2C12 myotube CM, but not by C2C12 myoblast CM. Moreover, survival of MLO-Y4 cells in the presence of dexamethasone is increased if cells were pre-exposed to CM from primary skeletal muscles subjected to ex vivo contractility. As little as 1% of CM blocked apoptosis showing high potency of a soluble factor(s). The responsible factor(s) appears to be less than 10kDa and identification studies are underway. These in vitro data show that skeletal muscle cells produce factors that prevent osteocyte cell death suggesting that skeletal muscles promote the maintenance of bone mass independent of loading. Support: NIH RC2 AR058962 and Missouri Life Sciences Research Board.