{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:39:01Z","timestamp":1791153541461,"version":"4.1.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,6,19]]},"abstract":"<jats:p>\n                    Bone is accrued and maintained primarily through the coupled actions of bone-forming osteoblasts and bone-resorbing osteoclasts. Cumulative\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies indicated that proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of osteoclast function and activity. However, our investigation of PYK2\u2212\/\u2212 mice did not reveal evidence supporting an essential function for PYK2 in osteoclasts either\n                    <jats:italic>in vivo<\/jats:italic>\n                    or in culture. We find that PYK2\u2212\/\u2212 mice have high bone mass resulting from an unexpected increase in bone formation. Consistent with the\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings, mouse bone marrow cultures show that PYK2 deficiency enhances differentiation and activity of osteoprogenitor cells, as does expressing a PYK2-specific short hairpin RNA or dominantly interfering proteins in human mesenchymal stem cells. Furthermore, the daily administration of a small-molecule PYK2 inhibitor increases bone formation and protects against bone loss in ovariectomized rats, an established preclinical model of postmenopausal osteoporosis. In summary, we find that PYK2 regulates the differentiation of early osteoprogenitor cells across species and that inhibitors of the PYK2 have potential as a bone anabolic approach for the treatment of osteoporosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0701421104","type":"journal-article","created":{"date-parts":[[2007,5,30]],"date-time":"2007-05-30T20:49:12Z","timestamp":1180558152000},"page":"10619-10624","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":137,"title":["Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis"],"prefix":"10.1073","volume":"104","author":[{"given":"Leonard","family":"Buckbinder","sequence":"first","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Crawford","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Qi","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua Zhu","family":"Ke","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Chesterfield, MO 63198"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly R.","family":"Long","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Chesterfield, MO 63198"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Bonnette","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy P.","family":"Baumann","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Hambor","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William A.","family":"Grasser","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia C.","family":"Pan","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Owen","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Luzzio","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Hulford","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Gebhard","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwas M.","family":"Paralkar","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollis A.","family":"Simmons","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Kath","sequence":"additional","affiliation":[{"name":"*Pfizer Global Research and Development, Groton, CT 06340; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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