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• W2003669078 abstract "Abstract Regulatory mechanisms operative in bone‐resorbing osteoclasts are complex. We previously defined the Ly‐6 gene family member OIP‐1/hSca as an inhibitor of osteoclastogenesis in vitro ; however, a role in skeletal development is unknown. In this study, we developed transgenic mice with OIP‐1/hSca expression targeted to the osteoclast lineage that develop an osteopetrotic bone phenotype. Humeri from OIP‐1 mice showed a significant increase in bone mineral density and bone mineral content. µCT analysis showed increased trabecular thickness and bone volume. OIP‐1 mice have dense sclerotic cortical bone with absence of spongiosa and inadequate formation of marrow spaces compared to wild‐type mice. Moreover, complete inhibition of osteoclasts and marrow cavities in calvaria suggests defective bone resorption in these mice. OIP‐1 mouse bone marrow cultures demonstrated a significant decrease (41%) in osteoclast progenitors and inhibition (39%) of osteoclast differentiation/bone resorption. Western blot analysis further demonstrated suppression of TRAF‐2, c‐Fos, p‐c‐Jun, and NFATc1 levels in RANKL‐stimulated osteoclast precursors derived from OIP‐1 mice. Therefore, OIP‐1 is an important physiological inhibitor of osteoclastogenesis and may have therapeutic value against bone loss in vivo . Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd." @default.
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• W2003669078 date "2007-10-16" @default.
• W2003669078 modified "2023-09-30" @default.
• W2003669078 title "Transgenic mice with OIP-1/hSca overexpression targeted to the osteoclast lineage develop an osteopetrosis bone phenotype" @default.
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• W2003669078 doi "https://doi.org/10.1002/path.2241" @default.
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