title: Spleen tyrosine kinase suppresses osteoblastic differentiation through MAPK and PKCα.
abstract: Spleen tyrosine kinase (Syk) is a non-receptor protein kinase present in abundance in a wide range of hematopoietic cells. Syk reportedly plays a crucial role in immune signaling in B cells and cells bearing Fcγ-activation receptors. The role of syk in osteoblastic differentiation has not been well elucidated. We report herein the role of syk in osteoblastic differentiation. We investigated the effects of two syk inhibitors on osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. Expression of syk was detected in these two cell lines. Two syk inhibitors stimulated mRNA expression of osteoblastic markers (ALP, Runx2, Osterix). Mineralization of extracellular matrix was also promoted by treatment with syk inhibitors. Knockdown of Syk caused increased mRNA expression of osteoblastic markers. In addition, syk inhibitor and knockdown of Syk suppressed phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase Cα (PKCα). Our results indicate that syk might regulate osteoblastic differentiation through MAPK and PKCα.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Chikahisa
authors.initials: C
authors.lastname: Higuchi
authors.forename: Akio
authors.initials: A
authors.lastname: Nakura
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology; D010012:Osteogenesis; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051571:Protein Kinase C-alpha; D020929:Mitogen-Activated Protein Kinase Kinases