Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin
作者： Alexander G. Robling , Paul J. Niziolek , Lee A. Baldridge , Keith W. Condon , Matthew R. Allen
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摘要: Sclerostin, the protein product of Sost gene, is a potent inhibitor bone formation. Among cells, sclerostin found nearly exclusively in osteocytes, cell type that historically has been implicated sensing and initiating mechanical signaling. The recent discovery antagonistic effects on Lrp5 receptor signaling, crucial mediator skeletal mechanotransduction, provides potential mechanism for osteocytes to control by adjusting their (Wnt inhibitory) signal output modulate Wnt signaling effector population. We investigated mechanoregulation under enhanced (ulnar loading) reduced (hindlimb unloading) loading conditions. transcripts levels were dramatically ulnar loading. Portions cortex receiving greater strain stimulus associated with reduction staining intensity sclerostin-positive (revealed via situ hybridization immunohistochemistry, respectively) than lower portions tissue. Hindlimb unloading yielded significant increase expression tibia. Modulation appears be finely tuned which coordinate regional local osteogenesis response increased stimulation, perhaps releasing inhibition Wnt/Lrp5
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