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Parathyroid-hormone-related Protein Induces Expression of Receptor Activator of NF-B Ligand in Human Periodontal Ligament Cells via a cAMP/Protein Kinase A-independent Pathway

¹ Department of Physiological Science and Molecular Biology and
² Department of Oral Growth and Development, Fukuoka Dental College, Tamura 2-15-11, Sawara-ku, Fukuoka 814-0193, Japan;

Correspondence: ^* corresponding author, ejimi{at}college.fdcnet.ac.jp

Periodontal ligament (PDL) cells play important roles in root resorption of human deciduous teeth by odontoclasts (osteoclast-like cells). However, it is unclear how PDL cells regulate osteoclastogenesis. We examined the effects of PTHrP, TGF-β, and EGF, which are all secreted by the tooth germ, on tartrate-resistant acid-phosphatase-positive (TRAP⁺) cell formation using co-cultures of human PDL cells and mouse spleen cells. Only PTHrP promoted TRAP⁺ cell formation in co-cultures. PTHrP induced receptor activator of NF-B ligand (RANKL) mRNA expression and slightly reduced osteoprotegerin (OPG) expression in PDL cells. The cAMP/PKA inhibitors Rp-cAMP, H89, and PKI did not affect PTHrP-induced TRAP⁺ cell formation. The PKC inhibitor, Ro-32-0432, suppressed RANKL expression in PDL cells and PTHrP-induced TRAP⁺ cell formation. However, this inhibitor directly modulated the number of osteoclast precursors. Thus, PTHrP induces osteoclastogenesis by increasing the relative expression level of RANKL vs. OPG in PDL cells via a cAMP/PKA-independent pathway. Abbreviations: PTHrP, parathyroid-hormone-related protein; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; RANKL, receptor activator of NF-B ligand; OPG, osteoprotegerin; PDL, periodontal ligament; TRAP, tartrate-resistant acid phosphatase; PKA, protein kinase A; PKC, protein kinase C; MAP, mitogen-activated protein; ERK, extracellular signal-regulated kinase; cAMP, cyclic Adenosine 3'5'-Monophosphate.

Key Words: PTHrP • periodontal ligament • osteoclast • PKA • PKC

Journal of Dental Research, Vol. 84, No. 4, 329-334 (2005)
DOI: 10.1177/154405910508400407


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