Journal
JOURNAL OF PERIODONTOLOGY
Volume 75, Issue 9, Pages 1247-1254Publisher
WILEY
DOI: 10.1902/jop.2004.75.9.1247
Keywords
cementoblasts; ligand, NF-kappa B; osteoblasts; osteoclasts; osteoprotegerin; proteins, parathyroid hormone related; receptor activator, NF-kappa B; tooth eruption; tooth root
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Funding
- NIDCR NIH HHS [DE14073, DE09532] Funding Source: Medline
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Background: Parathyroid hormone-related protein (PTHrP) promotes osteoclastogenesis by inhibiting expression of osteoprotegerin (OPG), a decoy receptor for the receptor activator of nuclear factor kappa B (RANK), and by enhancing production of RANK ligand (RANKL) by osteoblasts. However, little is known regarding the role of PTHrP in regulating cementoblast-mediated osteoclastogenesis. Methods: This study determined the impact of PTHrP on osteoclastogenesis using: 1) OCCM-30 (immortalized murine cemento-blasts), 2) RAW 264.7 cells (murine myeloid cells), or 3) OCCM-30 plus RAW 264.7 cells. Cells were treated with PTHrP (1-34), RANKL, or PTHrP and RANKL combined. Enzyme-linked immuno-sorbent assays (ELISAs) for OPG and RANKL were performed on media and cell lysates, and tartrate-resistant acid phosphatase (TRAP) and mRNA detection for the osteoclast associated receptor (OSCAR) were performed. Results: The highest numbers of TRAP-positive cells and cells expressing OSCAR were found in the RAW cell group treated with either RANKL alone or RANKL and PTHrP. TRAP-positive cells were fewer when OCCM cells were co-cultured with RAW, but the greatest numbers were still with both PTHrP and RANKL. OPG levels were highest from OCCM cells and PTHrP decreased these levels. In contrast, RANKL levels were low in OCCM cell lysates and PTHrP increased RANKL. In vivo studies also revealed high osteoclastic activity surrounding developing teeth in mice administered PTH. Conclusions: These results demonstrate that PTHrP influences the balance of OPG and RANKL production by cementoblasts, and further indicate that this effect, in the context of surrounding cells, might have a significant impact on osteoclastogenesis, root resorption, and tooth eruption.
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