Local injection of abaloparatide promotes mandibular condyle lengthening in adolescent rats via enhancing chondrogenesis and ossification

J Oral Rehabil. 2024 Feb;51(2):380-393. doi: 10.1111/joor.13597. Epub 2023 Sep 19.

Abstract

Background: Mandibular condylar hypoplasia negatively affects patient's facial appearance and dentofacial function.

Objective: To investigate the effect of local injection of the drug abaloparatide (ABL), an analogue of parathyroid hormone related protein (PTHrP), on promoting lengthening of the mandibular condyle.

Methods: Thirty adolescent male Sprague-Dawley rats were randomly divided into two groups, which received the injection of ABL or normal saline (the control) every 3 days in the temporomandibular joint (TMJ) cavity. Cone-beam computed tomography and immunohistochemistry assays were performed at 2, 4 and 6 weeks since the injection. Mandibular condylar chondrocytes (MCC) and pre-osteoblasts were treated with ABL or PBS, followed by the CCK-8 detection, IC50, real-time PCR assay, Western Blot and immunofluorescence staining.

Results: In vivo, compared with the control, the ABL group significantly increased the mandibular condylar process length (by 1.34 ± 0.59 mm at 6 weeks), the thickness of the cartilage layer, and enhanced the matrix synthesis. The ABL group had significant up-regulation of SOX 9, COL II, PTHrP and PTH1R, down-regulation of COL X in the cartilage, up-regulation of RUNX 2, and unchanged osteoclastogenesis in the subchondral bone. In vitro, the intra-TMJ injection of ABL promoted the MCC proliferation, with up-regulated expression of chondrogenic genes, and enhanced osteogenic differentiation of the pre-osteoblasts.

Conclusions: Intra-TMJ injection of abaloparatide promotes mandibular condyle lengthening in the adolescent rats via enhancing chondrogenesis in the mandibular condylar cartilage and ossification in the subchondral bone.

Keywords: PTHrP; abaloparatide; mandibular condylar chondrocyte; mandibular condyle; mandibular hypoplasia.

MeSH terms

  • Adolescent
  • Animals
  • Chondrocytes / metabolism
  • Chondrogenesis
  • Humans
  • Injections, Intra-Articular
  • Male
  • Mandibular Condyle* / metabolism
  • Osteogenesis
  • Parathyroid Hormone-Related Protein* / metabolism
  • Parathyroid Hormone-Related Protein* / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • abaloparatide
  • Parathyroid Hormone-Related Protein