Parathyroid-hormone-related protein induces expression of receptor activator of NF-{kappa}B ligand in human periodontal ligament cells via a cAMP/protein kinase A-independent pathway.
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-beta, 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-kappaB 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.


BACKGROUND
PTHrP, parathyroid-hormone-related protein; TGF-beta, transforming growth factor-beta; EGF, epidermal growth factor; RANKL, receptor activator of NF-kappaB 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.
Fukushima
H
H
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura 2-15-11, Fukuoka, Japan.
Jimi
E
E
Kajiya
H
H
Motokawa
W
W
Okabe
K
K
D000135:Acid Phosphatase; D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D000071681:Tartrate-Resistant Acid Phosphatase; D014078:Tooth Eruption / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase