{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T15:54:56Z","timestamp":1700495696985},"reference-count":36,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:p>Osteoclast inhibitory peptide-1 (OIP) is an autocrine\/paracrine inhibitor of osteoclast differentiation, and mice that overexpress OIP-1 in osteoclast lineage cells develop an osteopetrosis bone phenotype. In this study, we show that OIP-1 binding to the Fc\u03b3 receptor IIB (Fc\u03b3RIIB) inhibits osteoclast differentiation. Confocal microscopy revealed colocalization of OIP-1 with Fc\u03b3RIIB in osteoclasts, and we observed that OIP-1 carboxy-terminal GPI-linked peptide forms a 1:1 complex with recombinant Fc\u03b3RIIB protein with an affinity binding of a dissociation constant of approximately 4 \u03bcm. Immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter proteins (FcR\u03b3 and DNAX-activating protein of molecular mass 12 kDa) are critical for osteoclast development, and OIP-1 transgenic mouse-derived preosteoclast cells demonstrated suppression (6-fold) of ITAM phosphorylation of FcR\u03b3 but not DNAX-activating protein of molecular mass 12 kDa. Interestingly, these preosteoclast cells demonstrated increased levels (4-fold) of immunoreceptor tyrosine-based inhibitory motif phosphorylation of Fc\u03b3RIIB and Src homology 2-domain-containing proteins tyrosine phosphatase 1 activation. Further, OIP-1 mouse-derived preosteoclasts cells demonstrated inhibition of spleen tyrosine kinase activation (4.5-fold), compared with wild-type mice. These results suggest that cross-regulation of immunoreceptor tyrosine-based inhibitory motif and ITAM bearing Fc receptors may play a role in OIP-1 suppression of spleen tyrosine kinase activation and inhibition of osteoclast differentiation. Thus, OIP-1 is an important physiologic regulator of osteoclast development and may have therapeutic utility for bone diseases with high bone turnover.<\/jats:p>","DOI":"10.1210\/en.2010-0244","type":"journal-article","created":{"date-parts":[[2010,7,8]],"date-time":"2010-07-08T02:49:37Z","timestamp":1278557377000},"page":"4389-4399","source":"Crossref","is-referenced-by-count":6,"title":["Osteoclast Inhibitory Peptide-1 Binding to the Fc\u03b3RIIB Inhibits Osteoclast Differentiation"],"prefix":"10.1210","volume":"151","author":[{"given":"Srinivasan","family":"Shanmugarajan","sequence":"first","affiliation":[{"name":"Charles P. 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