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Sci. Signal., 21 December 2010
Vol. 3, Issue 153, p. ra91
[DOI: 10.1126/scisignal.2001423]

RESEARCH ARTICLES

Editor's Summary

Building Bone
The loss of bone density that afflicts individuals with osteoporosis makes them more vulnerable to bone fractures. One way to counteract decreases in bone density is through exercise, which mechanically stimulates bone tissue and initiates proliferation in bone-forming cells. Alternatively, the signaling pathways that mediate this proliferative response could be therapeutically activated to mimic the effects of mechanical stimulation. Nitric oxide (NO) is a second messenger that is produced in response to mechanical stimulation; it triggers production of cyclic GMP (cGMP) and, consequently, activation of protein kinase G (PKG). Rangaswami et al. delineated a pathway in mechanically stimulated osteoblasts whereby activation of PKGII signaling ultimately leads to a proliferative response. Mechanical stimuli triggered the formation of a complex containing PKGII, the tyrosine kinase Src, the phosphatases SHP-1 and SHP-2, and β3 integrin mechanoreceptors. Activation of Src in this complex led to activation of extracellular signal–regulated kinase (ERK), which in turn elicited changes in gene expression that promote proliferation. Thus, PKG-activating drugs could be used to mimic the anabolic effects of mechanical stimulation on bone in the treatment of osteoporosis. The accompanying Perspective by Bidwell and Pavalko describes other examples of signaling pathways that mediate mechanotransduction in bone cells.

Citation: H. Rangaswami, R. Schwappacher, N. Marathe, S. Zhuang, D. E. Casteel, B. Haas, Y. Chen, A. Pfeifer, H. Kato, S. Shattil, G. R. Boss, R. B. Pilz, Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts. Sci. Signal. 3, ra91 (2010).

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