{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:52:28Z","timestamp":1761094348408,"version":"build-2065373602"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T00:00:00Z","timestamp":1192492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regulatory mechanisms operative in bone\u2010resorbing osteoclasts are complex. We previously defined the <jats:italic>Ly\u20106<\/jats:italic> gene family member OIP\u20101\/hSca as an inhibitor of osteoclastogenesis <jats:italic>in vitro<\/jats:italic>; however, a role in skeletal development is unknown. In this study, we developed transgenic mice with OIP\u20101\/hSca expression targeted to the osteoclast lineage that develop an osteopetrotic bone phenotype. Humeri from OIP\u20101 mice showed a significant increase in bone mineral density and bone mineral content. \u00b5CT analysis showed increased trabecular thickness and bone volume. OIP\u20101 mice have dense sclerotic cortical bone with absence of spongiosa and inadequate formation of marrow spaces compared to wild\u2010type mice. Moreover, complete inhibition of osteoclasts and marrow cavities in calvaria suggests defective bone resorption in these mice. OIP\u20101 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\u20102, c\u2010Fos, p\u2010c\u2010Jun, and NFATc1 levels in RANKL\u2010stimulated osteoclast precursors derived from OIP\u20101 mice. Therefore, OIP\u20101 is an important physiological inhibitor of osteoclastogenesis and may have therapeutic value against bone loss <jats:italic>in vivo<\/jats:italic>. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2241","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T11:17:46Z","timestamp":1192533466000},"page":"420-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Transgenic mice with OIP\u20101\/hSca overexpression targeted to the osteoclast lineage develop an osteopetrosis bone phenotype"],"prefix":"10.1002","volume":"213","author":[{"given":"S","family":"Shanmugarajan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Irie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Musselwhite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LL","family":"Key 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