J Korean Endocr Soc.  2009 Dec;24(4):223-226. 10.3803/jkes.2009.24.4.223.

Why to Keep Osteocytes Alive and How?

Affiliations
  • 1Professor of Anatomy and Cell Biology, Adjunct Professor of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Abstract

It has been long proposed that the osteocyte network continually compares present mechanical strains to usual levels of strain, and triggers signals to osteoclasts or osteoblasts resulting in bone loss or gain, as needed. Whereas physiological levels of mechanical stimulation maintain bone mass, too low or too high levels of strain induce bone resorption. One mechanism by which osteocytes may trigger bone resorption is by undergoing apoptosis. Either low or high levels of mechanical loading lead to increased prevalence of osteocyte apoptosis, which temporally precedes and is spatially associated with osteoclast recruitment and the subsequent increase in bone resorption[1,2]. A cause and effect relationship between osteocyte death and bone resorption has been demonstrated using a transgenic mouse model of inducible osteocyte ablation in which osteocyte apoptosis was sufficient to trigger osteoclast recruitment[3]. In addition, the normal osteoclastogenic response to unloading was missing in bones from osteocyte-depleted mice, confirming that osteocytes are indispensable for the skeletal adaptation to weightlessness. Because osteocyte apoptosis is inhibited not only by mechanical stimulation but also by estrogens and bisphosphonates, these findings raise the intriguing possibility that preservation of osteocyte viability contributes to the anti-remodeling properties of these agents.


MeSH Terms

Animals
Apoptosis
Bone Resorption
Diphosphonates
Estrogens
Mice
Mice, Transgenic
Osteoblasts
Osteoclasts
Osteocytes
Prevalence
Sprains and Strains
Weightlessness
Diphosphonates
Estrogens

Figure

  • Fig. 1 A signal some comprising integrins, cytoskeletal proteins and kinases, including the focal adhesion kinase FAK and Src, transduces physiological levels of mechanical stimulation into activation of the ERK pathway leading to osteocyte survival[15]. Reduced mechanical stimulation eliminates kinase-mediated survival signaling, thereby leading to osteocyte apoptosis[1]. Apoptotic osteocytes, in turn, become the beacons for osteoclast recruitment and the resulting increase in bone resorption and bone loss[3].


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