Role of matrix metalloproteinase-10 in the BMP-2 inducing osteoblastic differentiation

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Author(s)

    • Mao Li
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
    • Yano Masato
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
    • Kawao Naoyuki
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
    • Tamura Yukinori
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
    • Okada Kiyotaka
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
    • Kaji Hiroshi
    • Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama 589-8511, Japan

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a skeletal disorder with progressive heterotopic ossification in skeletal muscle. A mutation causing constitutive activation in a bone morphogenetic protein (BMP) type 1 receptor [ALK2(R206H)] is found in most patients with FOP. However, the details in the heterotopic ossification of muscle in FOP and the role of matrix metalloproteinase-10 (MMP-10) in bone remain to be fully elucidated. In the present study, we investigated the role of MMP-10 in the differentiation of mouse myoblastic C2C12 cells into osteoblasts. MMP-10 was extracted as a factor, whose expression was most extensively enhanced by ALK2 (R206H) transfection in C2C12 cells. MMP-10 significantly augmented the levels of Osterix, type 1 collagen, alkaline phosphatase (ALP) and osteocalcin mRNA as well as ALP activity enhanced by BMP-2 in C2C12 cells. Moreover, a reduction in endogenous MMP-10 levels by siRNA significantly decreased the levels of Runx2, Osterix, type 1 collagen, ALP and osteocalcin mRNA enhanced by BMP-2 in these cells. In addition, MMP-10 increased the phosphorylation of Smad1/5/8 as well as enhanced the levels of Smad6 and Smad7 mRNA induced by BMP-2. In conclusion, the present study first demonstrated that MMP-10 promotes the differentiation of myoblasts into osteoblasts by interacting with the BMP signaling pathway. MMP-10 may play some important role in the heterotopic ossification of muscle in FOP.

Journal

  • Endocrine Journal

    Endocrine Journal 60(12), 1309-1319, 2013

    The Japan Endocrine Society

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