{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:11:43Z","timestamp":1780103503968,"version":"3.54.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T00:00:00Z","timestamp":1506556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008593","name":"Japan Foundation for Aging and Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Bone marrow stromal cells (BMSCs) are multipotent cells that can differentiate into adipocytes and osteoblasts. Inadequate BMSC differentiation is occasionally implicated in chronic bone metabolic disorders. However, specific signaling pathways directing BMSC differentiation have not been elucidated. Here, we explored the roles of spleen tyrosine kinase (Syk) in BMSC differentiation into adipocytes and osteoblasts. We found that Syk phosphorylation was increased in the early stage, whereas its protein expression was gradually decreased during the adipogenic and osteogenic differentiation of two mouse mesenchymal stromal cell lines, ST2 and 10T(1\/2), and a human BMSC line, UE6E\u20107\u201016. Syk inactivation with either a pharmacological inhibitor or Syk\u2010specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the gene expression of <jats:italic>fatty acid protein 4<\/jats:italic> (<jats:italic>Fabp4<\/jats:italic>), <jats:italic>peroxisome proliferator\u2010activated receptor \u03b32 (Pparg2)<\/jats:italic>, <jats:italic>CCAAT\/enhancer binding proteins \u03b1 (C\/EBP\u03b1)<\/jats:italic>, and <jats:italic>C\/EBP\u03b2<\/jats:italic>. In contrast, Syk inhibition promoted osteogenic differentiation, represented by increase in matrix mineralization and alkaline phosphatase (ALP) activity, as well as the expression levels of <jats:italic>osteocalcin<\/jats:italic>, <jats:italic>runt\u2010related transcription factor 2 (Runx2)<\/jats:italic>, and <jats:italic>distal\u2010less homeobox 5 (Dlx5)<\/jats:italic> mRNAs. We also found that Syk\u2010induced signals are mediated by phospholipase C \u03b31 (PLC\u03b31) in osteogenesis and PLC\u03b32 in adipogenesis. Notably, Syk\u2010activated PLC\u03b32 signaling was partly modulated through B\u2010cell linker protein (BLNK) in adipogenic differentiation. On the other hand, growth factor receptor\u2010binding protein 2 (Grb2) was involved in Syk\u2010PLC\u03b31 axis in osteogenic differentiation. Taken together, these results indicate that Syk\u2010PLC\u03b3 signaling has a dual role in regulating the initial stage of adipogenic and osteogenic differentiation of BMSCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26130","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T11:22:52Z","timestamp":1502191372000},"page":"2549-2559","source":"Crossref","is-referenced-by-count":14,"title":["Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities"],"prefix":"10.1002","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-8089","authenticated-orcid":false,"given":"Joji","family":"Kusuyama","sequence":"first","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Kamisono","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong","family":"ChangHwan","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad S.","family":"Amir","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"},{"name":"Department of Oral and Maxillofacial Surgery Field of Oral and Maxillofacial Rehabilitation Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"},{"name":"Department of Oral and Maxillofacial Surgery Faculty of Dentistry Airlangga University Surabaya Indonesia"},{"name":"Campus A UNAIR, JL, Mayjen Professor Doktor Moestopo, Pacar Kembang, Tambaksari, Kota SBY, Jawa Timur Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Bandow","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Tissue Engineering Meikai University School of Dentistry Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahoko","family":"Eiraku","sequence":"additional","affiliation":[{"name":"Department of Periodontology Field of Oral and Maxillofacial Rehabilitation Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matsuguchi","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.023572"},{"issue":"249","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1126\/scisignal.2003576","article-title":"Grb2, a double\u2010edged sword of receptor tyrosine kinase signaling","volume":"5","author":"Belov A. 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