RRC ID 1255
著者 Mogi M, Togari A.
タイトル Activation of caspases is required for osteoblastic differentiation.
ジャーナル J Biol Chem
Abstract Previous studies have shown that mouse osteoblastic MC3T3-E1 cells undergo apoptosis when exposed to a mixture of proinflammatory cytokines. Bone morphogenetic protein (BMP)s are important regulators of osteoblast differentiation. Because regulation of osteoblastic differentiation is poorly understood, we sought to determine if BMP-4-induced differentiation of osteoblastic cells depends on the activity of the key apoptotic proteases, i.e. the caspases. BMP-4 induced the growth arrest and differentiation of osteoblastic cell line MC3T3-E1, as evidenced by the appearance of osteoblastic phenotypes such as alkaline phosphatase (ALP) activation and parathyroid hormone (PTH)-dependent production of cAMP. Surprisingly, BMP-4 induced transient and potent activation of caspase-8, caspase-2, and caspase-3, in this order. However, no apoptosis or necrosis in BMP-4-treated cells could be detected by FACS using annexin-V/propodium iodine double staining. Peptide inhibition of caspase activity led to a dramatic reduction in ALP activation and PTH-induced production of cAMP in BMP-4-treated cells. Although BMP-4 treatment resulted in cell-cycle G0/G1 arrest as detected by FACS cell-cycle analysis, caspase inhibitors (caspase-8, caspase-2, and caspase-3 inhibitors) could block the G0/G1 arrest in MC3T3-E1 cells. Taken together, these results confirm a unique and unanticipated role for the caspase-mediated signal cascade in the differentiation of osteoblasts.
巻・号 278(48)
ページ 47477-82
公開日 2003-11-28
DOI 10.1074/jbc.M307055200
PII S0021-9258(20)75770-4
PMID 12954609
MeSH Alkaline Phosphatase / metabolism Animals Apoptosis Blotting, Western Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins / metabolism Caspase 2 Caspase 3 Caspase 8 Caspase 9 Caspases / metabolism* Cell Cycle Cell Differentiation Cell Division Cell Line Cell Separation Cyclic AMP / metabolism Enzyme Activation Enzyme-Linked Immunosorbent Assay Flow Cytometry Mice Osteoblasts / cytology* Parathyroid Hormone / metabolism Phenotype Time Factors
IF 4.238
引用数 104
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)