4.3 Article

Intermittent Parathyroid Hormone [1-34] Augments Chondrogenesis of the Mandibular Condylar Cartilage of the Temporomandibular Joint

Journal

CARTILAGE
Volume 12, Issue 4, Pages 475-483

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/1947603519833146

Keywords

mandibular condylar cartilage; temporomandibular joint; parathyroid hormone

Categories

Funding

  1. National Institute of Dental and Craniofacial Research of the National Institute of Health [KO8DE025914]
  2. Connecticut Institute for Clinical and Translational Science Award
  3. American Association of Orthodontic Foundation

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I-PTH administration leads to increased bone volume, tissue density, mineral deposition, osteoclastic activity, cell proliferation, and cartilage thickness in the mandibular condylar cartilage (MCC). Additionally, I-PTH administration results in an increase in expression of vascular endothelial growth factor and a decrease in expression of sclerostin, matrix metallopeptidase 13, and aggreganase-1 (ADAM-TS4) in the cartilage. Molecular analysis shows decreased expression of collagen type X (Col10a1), alkaline phosphatase (Alp), and Indian Hedgehog (Ihh), and increased expression of Sox9, fibroblast growth factor 2 (Fgf2), and proteoglycan 4 (Prg4) in I-PTH-treated chondrocytes.
Objective To characterize the long-term effects of intermittent parathyroid hormone (I-PTH) on the mandibular condylar cartilage (MCC) and subchondral bone of the temporomandibular joint, in vivo and in vitro.Materials and Methods For the in vivo experiments, sixteen 10-week-old mice were divided into 2 groups: (1) I-PTH (n = 8)-subcutaneous daily injection of PTH; (2) control group (n = 8)-subcutaneous daily injection of saline solution. Experiments were carried out for 4 weeks. Mice were injected with calcein, alizarin complexone, and cell proliferation marker before euthanasia. For the in vitro experiments, primary chondrocyte cultures from the MCC of eight 10-week-old mice were treated with I-PTH for 14 days.Results There was a significant increase in bone volume, tissue density, mineral deposition, osteoclastic activity, cell proliferation in the cartilage, and cartilage thickness in the I-PTH-treated mice when compared with the control group. In addition, immunohistochemistry in cartilage revealed that I-PTH administration led to an increase in expression of vascular endothelial growth factor and to a decreased expression of sclerostin, matrix metallopeptidase 13, and aggreganase-1 (ADAM-TS4). Quantitative polymerase chain reaction analysis of the I-PTH-treated chondrocytes revealed significantly decreased relative expression of collagen type X (Col10a1), alkaline phosphatase (Alp), and Indian Hedgehog (Ihh) and remarkable increased expression of Sox9, fibroblast growth factor 2 (Fgf2), and proteoglycan 4 (Prg4).Conclusion I-PTH administration causes anabolic effects at the subchondral region of the mandibular condyle while triggers anabolic and protective effects at the MCC.

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