{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:21:33Z","timestamp":1793488893269,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,11]]},"abstract":"<jats:p>\n                    Clinical data showing correlations between low thyroid-stimulating hormone (TSH) levels and high bone turnover markers, low bone mineral density, and an increased risk of osteoporosis-related fractures are buttressed by mouse genetic and pharmacological studies identifying a direct action of TSH on the skeleton. Here we show that the skeletal actions of TSH deficiency are mediated, in part, through TNF\u03b1. Compound mouse mutants generated by genetically deleting the\n                    <jats:italic>Tnf<\/jats:italic>\n                    <jats:italic>\u03b1<\/jats:italic>\n                    gene on a\n                    <jats:italic>Tshr<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    (homozygote) or\n                    <jats:italic>Tshr<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    (heterozygote) background resulted in full rescue of the osteoporosis, low bone formation, and hyperresorption that accompany TSH deficiency. Studies using ex vivo bone marrow cell cultures showed that TSH inhibits and stimulates TNF\u03b1 production from macrophages and osteoblasts, respectively. TNF\u03b1, in turn, stimulates osteoclastogenesis but also enhances the production in bone marrow of a variant TSH\u03b2. This locally produced TSH suppresses osteoclast formation in a negative feedback loop. We speculate that TNF\u03b1 elevations due to low TSH signaling in human hyperthyroidism contribute to the bone loss that has traditionally been attributed solely to high thyroid hormone levels.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1308336110","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T01:46:29Z","timestamp":1369791989000},"page":"9891-9896","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Genetic confirmation for a central role for TNF\u03b1 in the direct action of thyroid stimulating hormone on the skeleton"],"prefix":"10.1073","volume":"110","author":[{"given":"Li","family":"Sun","sequence":"first","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Ling","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Yuen","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Pediatrics, Mount Sinai School of Medicine, New York, NY 10029;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risheng","family":"Ma","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Thyroid Research Unit, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumarie","family":"Baliram","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Thyroid Research Unit, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surinder S.","family":"Moonga","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberta","family":"Zallone","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Department of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"New","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Pediatrics, Mount Sinai School of Medicine, New York, NY 10029;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry F.","family":"Davies","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and"},{"name":"Departments of bMedicine and"},{"name":"Thyroid Research Unit, James J. 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