Parathyroid-hormone-related protein induces expression of receptor activator of NF-κB ligand in human periodontal ligament cells via a cAMP/protein kinase A-independent pathway

H. Fukushima, Eijiro Jimi, H. Kajiya, W. Motokawa, K. Okabe

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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-κB 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-κB 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.

Original languageEnglish
Pages (from-to)329-334
Number of pages6
JournalJournal of Dental Research
Volume84
Issue number4
DOIs
Publication statusPublished - Apr 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

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