{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:47:58Z","timestamp":1791175678095,"version":"4.1.0"},"reference-count":61,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,11,29]]},"abstract":"<jats:p>Matrix GLA protein (MGP), a \u03b3-carboxyglutamic acid (GLA)\u2013rich, vitamin K\u2013dependent and apatite-binding protein, is a regulator of hypertrophic cartilage mineralization during development. However, MGP is produced by both hypertrophic and immature chondrocytes, suggesting that MGP's role in mineralization is cell stage\u2013dependent, and that MGP may have other roles in immature cells. It is also unclear whether MGP regulates the quantity of mineral or mineral nature and quality as well. To address these issues, we determined the effects of manipulations of MGP synthesis and expression in (a) immature and hypertrophic chondrocyte cultures and (b) the chick limb bud in vivo. The two chondrocyte cultures displayed comparable levels of MGP gene expression. Yet, treatment with warfarin, a \u03b3-carboxylase inhibitor and vitamin K antagonist, triggered mineralization in hypertrophic but not immature cultures. Warfarin effects on mineralization were highly selective, were accompanied by no appreciable changes in MGP expression, alkaline phosphatase activity, or cell number, and were counteracted by vitamin K cotreatment. Scanning electron microscopy, x-ray microanalysis, and Fourier-transform infrared spectroscopy revealed that mineral forming in control and warfarin-treated hypertrophic cell cultures was similar and represented stoichiometric apatite. Virally driven MGP overexpression in cultured chondrocytes greatly decreased mineralization. Surprisingly, MGP overexpression in the developing limb not only inhibited cartilage mineralization, but also delayed chondrocyte maturation and blocked endochondral ossification and formation of a diaphyseal intramembranous bone collar. The results show that MGP is a powerful but developmentally regulated inhibitor of cartilage mineralization, controls mineral quantity but not type, and appears to have a previously unsuspected role in regulating chondrocyte maturation and ossification processes.<\/jats:p>","DOI":"10.1083\/jcb.147.5.1097","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"1097-1108","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":168,"title":["Matrix Gla Protein Is a Developmental Regulator of Chondrocyte Mineralization And, When Constitutively Expressed, Blocks Endochondral and Intramembranous Ossification in the Limb"],"prefix":"10.1083","volume":"147","author":[{"given":"Kimitoshi","family":"Yagami","sequence":"first","affiliation":[{"name":"aDepartment of Oral Surgery, Showa University, Dental School, Ohta-Ku, Tokyo 145, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Young","family":"Suh","sequence":"additional","affiliation":[{"name":"dDepartment of Anatomy-Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomi","family":"Enomoto-Iwamoto","sequence":"additional","affiliation":[{"name":"bDepartment of Biochemistry, Osaka University Faculty of Dentistry, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Koyama","sequence":"additional","affiliation":[{"name":"dDepartment of Anatomy-Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Abrams","sequence":"additional","affiliation":[{"name":"dDepartment of Anatomy-Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving M.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"eDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Pacifici","sequence":"additional","affiliation":[{"name":"dDepartment of Anatomy-Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"cDepartment of Oral Anatomy and Developmental Biology, Osaka University Faculty of Dentistry, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,11,29]]},"reference":[{"key":"2023072901021108600_Anderson1990","first-page":"13","article-title":"Biology of disease-mechanism of mineral formation in bone","volume-title":"Pathology Reviews","author":"Anderson","year":"1990"},{"key":"2023072901021108600_Baroneetal1991","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/jcb.240460410","article-title":"Developmental expression and hormonal regulation of the rat matrix GLA protein (MGP) gene in chondrogenesis and osteogenesis","volume":"46","author":"Barone","year":"1991","journal-title":"J. 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