{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:43:03Z","timestamp":1790232183254,"version":"4.1.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,3,16]]},"abstract":"<jats:p>Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-\u03b2 family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distal-less homeobox\u20135 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials.<\/jats:p>","DOI":"10.1073\/pnas.0911929107","type":"journal-article","created":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T23:55:41Z","timestamp":1267487741000},"page":"5124-5129","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":200,"title":["Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease"],"prefix":"10.1073","volume":"107","author":[{"given":"Sonia","family":"Vallet","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"MGH Center for Regenerative Medicine, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nileshwari","family":"Vaghela","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teru","family":"Hideshima","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Fulciniti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Boston, MA 02115;"},{"name":"Department of Medicine, Veterans Affairs Boston Health Care System, Boston, MA 02130;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Santo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Cirstea","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishan","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliyah R.","family":"Sohani","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Guimaraes","sequence":"additional","affiliation":[{"name":"Center for Systems Biology, Simches Research Facility, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; 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