{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:04Z","timestamp":1779696364604,"version":"3.53.1"},"reference-count":58,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T00:00:00Z","timestamp":1457308800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    All-\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    retinoic acid (ATRA) is a potent inducer of osteogenic differentiation in mouse adipose-derived stromal cells (mASCs), although the underlying mechanisms responsible for its mode of action have yet to be completely elucidated. High temperature requirement protease A1 (HtrA1) is a newly recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as such, may play a role in regulating ATRA-dependent osteogenic differentiation of mASCs. In this study, we assessed the influence of small interfering RNA (siRNA)-induced repression of HtrA1 production on mASC osteogenesis and examined its effects on ATRA-mediated mammalian target of rapamycin (mTOR) signaling. Inhibition of HtrA1 production in osteogenic mASCs resulted in a significant reduction of alkaline phosphatase activity and mineralized matrix formation. Western blot analyses revealed the rapid activation of Akt (Ser473) and p70S6K (Thr389) in ATRA-treated mASCs, and that levels of phosphorylated p70S6K were noticeably reduced in HtrA1-deficient mASCs. Further studies using mTOR inhibitor rapamycin and siRNA specific for the p70S6K gene\n                    <jats:italic toggle=\"yes\">Rps6kb1<\/jats:italic>\n                    confirmed ATRA-mediated mASC osteogenesis as being dependent on p70S6K activation. Finally, transfection of cells with a constitutively active rapamycin-resistant p70S6K mutant could restore the mineralizing capacity of HtrA1-deficient mASCs. These findings therefore lend further support for HtrA1 as a positive mediator of MSC osteogenesis and provide new insights into the molecular mode of action of ATRA in regulating mASC lineage commitment.\n                  <\/jats:p>","DOI":"10.1089\/scd.2015.0368","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T12:24:53Z","timestamp":1457353493000},"page":"687-698","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss-of-Function of HtrA1 Abrogates All-\n                    <i>Trans<\/i>\n                    Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation"],"prefix":"10.1177","volume":"25","author":[{"given":"Stephan","family":"Glanz","sequence":"first","affiliation":[{"name":"University of Zurich","place":["Switzerland"]},{"name":"University of 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