4.6 Article

Lamin A overexpression promotes osteoblast differentiation and calcification in the MC3T3-E1 preosteoblastic cell line

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.02.110

Keywords

Osteoblast differentiation; Nuclear lamina; Lamin A/C; Fulvestrant; BMP-2

Funding

  1. Dental Research Center, Nihon University School of Dentistry
  2. Uemura Fund, Nihon University School of Dentistry
  3. Sato Fund, Nihon University School of Dentistry
  4. JSPS KAKENHI [16K11462]
  5. Grants-in-Aid for Scientific Research [16K11462] Funding Source: KAKEN

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Lamin A/C is a component of the nuclear lamina, which is involved in cellular proliferation and differentiation. However, the mechanism by which lamin A regulates osteoblast differentiation is not well understood. In this study, we investigated lamin A/C expression during osteoblast differentiation in a preosteoblastic cell line, MC3T3-El. Real-time PCR analysis showed that lamin A/C mRNA expression was upregulated during BMP-2 induced osteoblast differentiation. Treatment with the estrogen receptor antagonist, fulvestrant, inhibited osteoblast differentiation and the upregulation of lamin A/C mRNA and protein expressions in the presence of BMP-2. These results clearly demonstrated that lamin A/C expression correlates with osteoblast differentiation. To determine the roles of lamin A expression in osteoblast differentiation, MC3T3-E1 cells were transfected with a vector overexpressing lamin A. Results showed that lamin A overexpression promoted osteoblast differentiation and calcification by inducing the expression of alkaline phosphatase, type I collagen, BSP, osteocalcin, and DMP-1 in the presence of BMP-2. Furthermore, lamin A overexpression partially restored osteoblastic capacity in the presence of fulvestrant by increasing the expression of BSP, osteocalcin, and DMP-1. These results suggest that lamin A plays important roles in maintaining the osteoblast differentiation and function. (C) 2017 Elsevier Inc. All rights reserved.

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