The role of parathyroid hormone-related protein in the regulation of osteoclastogenesis by cementoblasts.
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 cementoblasts), 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 immunosorbent 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.
Boabaid
Fernanda
F
Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Berry
Janice E
JE
Koh
Amy J
AJ
Somerman
Martha J
MJ
McCcauley
Laurie K
LK
D000135:Acid Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000166:cytology / Q000187:drug effects; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D003739:Dental Cementum / Q000166:cytology / Q000187:drug effects*; D006023:Glycoproteins / Q000032:analysis / Q000037:antagonists & inhibitors; D007527:Isoenzymes / Q000032:analysis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor; D000071681:Tartrate-Resistant Acid Phosphatase; D019379:Teriparatide / Q000494:pharmacology*; D014083:Tooth Germ / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C450519:Oscar protein, mouse; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase