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Effects of Parathyroid Hormone (PTH) and PTH-Related Peptide on Expressions of Matrix Metalloproteinase- 2, -3, and -9 in Growth Plate Chondrocyte Cultures¹

Departments of Biochemistry (Y.K.-O.,T.K., M.N., Y.Ka.), Removable Prosthodontics (H.S., Y.A.), and Endodontology and Periodontology (S.N.), Hiroshima University School of Dentistry, Hiroshima 734; the Department of Orthopedic Surgery, Faculty of Medicine, the University of Tokyo (Y.Ku.), Tokyo 113; the Department of Biochemistry, Aichi-Gakuin University School of Dentistry (T.H.), Nagoya 464; and the Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University (Y.O.), Kanazawa 920, Japan; and the Department of Biochemistry, Institute of Endemic Disease, Norman Bethune University of Medical Sciences (W.Y.), Changchun 1300–21, China

Address all correspondence and requests for reprints to: Dr. Yukio Kato, Department of Biochemistry, Hiroshima University School of Dentistry, 1–2-3 Kasumi, Minami-ku, Hiroshima 734, Japan. E-mail: ykato{at}ipc.hiroshima-u.ac.jp

The roles of PTH and PTH-related peptide (PTH-rp) in the expression of matrix metalloproteinases (MMPs) during endochondral bone formation were investigated, using various cartilages obtained from young rabbits and rabbit chondrocyte cultures. Immunohistochemical, immunoblotting, zymographical, and/or Northern blot analyses showed that MMP-2 and -9 levels were much higher in the growth plate than in permanent cartilage in vivo. In growth plate chondrocyte cultures, PTH, PTH-rp, and (Bu)₂cAMP increased the amount of MMP-2 present in the culture medium, as revealed by zymograms and immunoblots, whereas the other tested growth factors or cytokines, including bone morphogenetic protein-2 and interleukin-1, did not increase the MMP-2 level. PTH also increased the MMP-2 messenger RNA level within 24 h. In addition, PTH increased MMP-3 and -9 levels in the growth plate chondrocyte cultures. However, in articular chondrocyte cultures, PTH had little effect on the levels of MMP-2, -3, and -9. In contrast to PTH, interleukin-1 induced MMP-3 and -9, but not MMP-2, in growth plate and articular chondrocytes. These findings suggest that in ossifying cartilage, PTH/PTH-rp plays a pivotal role in the induction of various MMPs, including MMP-2 (which is considered to be a constitutive enzyme), and that PTH/PTH-rp is involved in the control of cartilage-matrix degradation during endochondral bone formation.

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