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J. Biol. Chem., Vol. 278, Issue 37, 35743-35748, September 12, 2003

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The Receptor Activator of Nuclear Factor-B Ligand-mediated Osteoclastogenic Pathway Is Elevated in Amelogenin-null Mice^*

Junko Hatakeyama , Taduru Sreenath , Yuji Hatakeyama , Tamizchelvi Thyagarajan , Lillian Shum , Carolyn W. Gibson ¶, J. Tim Wright || and Ashok B. Kulkarni  **

From the Functional Genomics Unit, NIDCR and the Cartilage Biology and Orthopaedics Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, the ^¶Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania 19104, and the ^||Department of Pediatric Dentistry, University of North Carolina, Chapel Hill, North Carolina 27599

Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide (LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-B ligand (RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.

Received for publication, June 13, 2003 , and in revised form, July 7, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bldg. 30, Rm. 527, Bethesda, MD 20892. Tel.: 301-435-2887; Fax: 301-435-2888; E-mail: ak40m{at}nih.gov.

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