{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T08:58:19Z","timestamp":1775293099964,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T00:00:00Z","timestamp":1543795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500874"],"award-info":[{"award-number":["81500874"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cleidocranial dysplasia (CCD) in humans is an autosomal\u2010dominant skeletal dysplasia caused by heterozygous mutations of the runt\u2010related transcription factor 2 (\n                      <jats:italic>RUNX2<\/jats:italic>\n                      ) and significantly increases the risk of osteoporosis. Increasing evidence demonstrates that the dysfunction of bone marrow stromal cells from CCD patients (BMSCs\u2010CCD) contributes to the bone deficiency, but the characteristics of BMSCs\u2010CCD and the mechanisms that underlie their properties remain undefined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The clinical manifestations of three CCD patients were collected and the mutations of\n                      <jats:italic>RUNX2<\/jats:italic>\n                      were analyzed. The properties of proliferation, osteogenesis, stemness, and senescence of BMSCs\u2010CCD were compared with that of BMSCs from healthy donors. The expression of microRNA\u201031 (\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      ) between BMSCs\u2010CCD and BMSCs was measured and lentivirus\u2010carried\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      inhibitor was used to determine the role of\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      in BMSCs\u2010CCD both in vitro and in vivo. The molecular mechanisms underlying RUNX2\u2010miR31 and\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      targeting stemness and senescence of BMSCs\u2010CCD were also explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified two mutation sites of\n                      <jats:italic>RUNX2<\/jats:italic>\n                      via exome sequencing from 2 of 3 Chinese CCD patients with typical clinical presentations. Compared with BMSCs from healthy donors, BMSCs\u2010CCD displayed significantly attenuated proliferation, osteogenesis and stemness, and enhanced senescence. Meanwhile,\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      knockdown could ameliorate these deficiency phenotypes of BMSCs\u2010CCD by regulating\n                      <jats:italic>SATB2<\/jats:italic>\n                      ,\n                      <jats:italic>BMI1<\/jats:italic>\n                      ,\n                      <jats:italic>CDKN<\/jats:italic>\n                      , and\n                      <jats:italic>SP7<\/jats:italic>\n                      . Mechanistically,\n                      <jats:italic>RUNX2<\/jats:italic>\n                      directly repressed\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      expression, and therefore\n                      <jats:italic>RUNX2<\/jats:italic>\n                      haploinsufficiency in CCD leading to\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      upregulation contributed to the deficiency of BMSCs\u2010CCD.\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      inhibition in BMSCs\u2010CCD showed enhanced osteogenesis through heterotopic subcutaneous implantation in the nude mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results show the functional deficiencies of BMSCs\u2010CCD and a potential role of\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      in BMSCs\u2010CCD deficiencies. The application of\n                      <jats:italic>miR\u201031<\/jats:italic>\n                      inhibitor in BMSCs\u2010CCD might lend hope for developing BMSC\u2010based therapeutic approaches against CCD\u2010associated skeletal diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcb.28223","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T03:16:00Z","timestamp":1543806960000},"page":"9472-9486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["microRNA\u201031 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia"],"prefix":"10.1002","volume":"120","author":[{"given":"Ling","family":"Xu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases Nanjing Medical University Nanjing China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated 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