{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:22:44Z","timestamp":1789039364976,"version":"build-2803163510"},"reference-count":75,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"710","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,8,23]]},"abstract":"<jats:p>\n            Sulfation is a widespread modification of biomolecules that has been incompletely explored to date. Through cross-phenotype meta-analysis of bone mineral density in up to 426,824 genotyped human participants along with phenotypic characterization of multiple mutant mouse lines, we identified a causative role for sulfate transporter solute carrier family 26 member A2 (\n            <jats:italic>SLC26A2<\/jats:italic>\n            ) deficiency in osteoporosis. Ablation of\n            <jats:italic>SLC26A2<\/jats:italic>\n            in osteoblasts caused severe bone loss and accumulation of immature bone cells and elicited peculiar pericellular matrix (PCM) production characterized by undersulfation coupled with decreased stiffness. These altered chemophysical properties of the PCM disrupted the formation of focal adhesions in osteoblasts. Bulk RNA sequencing and functional assays revealed that the mechanoreciprocal inhibition of focal adhesion kinase (FAK) and Yes1-associated transcriptional regulator (YAP)\/WW domain containing transcription regulator 1 (TAZ) signaling impinged osteoblast maturation upon\n            <jats:italic>SLC26A2<\/jats:italic>\n            deficiency. Moreover, pharmacological abrogation of the Hippo kinases and forced wheel-running ameliorated\n            <jats:italic>SLC26A2<\/jats:italic>\n            -deficient osteoporosis by promoting YAP\/TAZ activity. Analysis of mouse single-cell RNA sequencing data suggested coordination among sulfate metabolism, focal adhesion, and YAP\/TAZ activity during osteoblast-to-osteocyte transition. In addition to the\n            <jats:italic>SLC26A2<\/jats:italic>\n            -deficient setting, altered FAK and YAP\/TAZ signaling was also observed in bone cells of ovariectomized mice and patients with osteoporosis, and pharmacological enforcing of YAP\/TAZ activity ameliorated bone loss in ovariectomized mice. Collectively, these data unveil a role for sulfation in the developmental mechanoreciprocity between matrix and osteoblasts, which could be leveraged to prevent bone loss.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adg3983","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T17:58:18Z","timestamp":1692813498000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["Targeting sulfation-dependent mechanoreciprocity between matrix and osteoblasts to mitigate bone loss"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8530-0923","authenticated-orcid":true,"given":"Chao","family":"Zheng","sequence":"first","affiliation":[{"name":"Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, 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