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Volume 8 Journal of Biotechnology & Biomaterials
ISSN: 2155-952X Biotech Congress 2018 & Enzymology 2018
March 05-07, 2018
JOINT EVENT
20th Global Congress on Biotechnology
3rd International Conference on Enzymology and Molecular Biology
&
March 05-07, 2018 London, UK
Osteocyte-specific Cas knockout mice exhibit decreased bone mass through increased osteoclastic
bone resorption
Tsuyoshi Miyazaki1, Fumiaki Tokimura1 and Yasuhiro Sawada2
1Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Japan
2National Rehabilitation Center for Persons with Disabilities, Japan
The skeleton is a metabolically active organ that undergoes continuous remodeling throughout life. Osteoporosis, which
is fostered by advancing age, is the most common clinical disorder affecting bones. Although it has been postulated
that osteocytes play an important role in sensing mechanical load in bone tissues, detailed molecular mechanisms of how
osteocytes regulate bone metabolism remain largely unclear. The adaptor molecule p130Cas (Crk-associated substrate,
hereafter referred to as Cas), which is phosphorylated at focal adhesions upon extracellular matrix engagement, is involved in
various cellular processes including migration, survival, transformation, and invasion. In addition, we reported that Cas binds
to the cytoskeletons in a stretch-dependent manner. This suggests that Cas can function as an initiator of intracellular signaling
cascades through force-dependent changes in the cytoskeleton network. To investigate the role of Cas in bone metabolism,
we generated osteocyte-specific Cas conditional knockout (cKO) mice by mating Casflox/flox mice with Dentin matrix protein 1
(Dmp1)-Cre transgenic mice, in which the Cre recombinase gene was specifically expressed in osteocytes. The resulting Dmp1-
Cre+/–; Casflox/flox mice (referred to herein as Cas cKO mice) exhibited a significant decrease in bone volume, as determined
by µCT analysis. Histomorphometric analysis of Cas cKO mice revealed a significant increase in the eroded surface/bone
surface ratio, osteoclast surface, and osteoclast number. Furthermore, the expression levels of RANKL genes were significantly
increased in the osteocyte fractions derived from Cas cKO mice. Collectively, these findings suggest that the bone loss in Cas
cKO mice was caused by increased osteoclatstic bone resorption.
J Biotechnol Biomater 2018, Volume 8
DOI: 10.4172/2155-952X-C2-092