IADR Abstract Archives

Attenuation of Condylar Cartilage Degeneration by Genetic Inactivation of HtrA1

Objectives: The objective of this investigation is to determine whether or not the deletion of a serine protease, high temperature requirement A1 (HTRA1), can significantly delay the process of condylar cartilage degeneration. The expression of HTRA1 is increased in human osteoarthritic cartilages and cartilages of mouse models of osteoarthritis (OA). The increased expression of HtrA1 was associated with the degradation of the pericellular matrix of chondrocytes and the up-regulated expression of matelloproteinase 13 (MMP-13). Based on the aforementioned finds, we hypothesize that the removal of HTRA1 can protect the pericellular matrix from being degraded and maintain the homeostasis of chondrocyte metabolism. This, in turn, inhibits induction of MMP-13.
Methods: Experimental methods used in this study included the deletion of HtrA1 in mice (HtrA1-/-) by the conventional knockout techniques; the induction of condylar cartilage degeneration by either a partial discectomy of temporomandibular joint (TMJ) on HtrA1-/- mice (HtrA1-/-/PDE), or by the type XI collagen-haploinsufficiency in HtrA1-/- mice (HtrA1-/-;Col11a1+/-). For surgical model, HtrA1-/-/sham and partial discectomy on wild type (WT/PDE) mice were controls. For genetic model, Col11a1+/- mice and wild-type littermates were controls. The condition of condylar cartilages in each group (n=4) was characterized by histology and immunohistochemistry and evaluated by a modified Mankin score system.
Results: Results from histology showed that the damage of condylar cartilage in HtrA1-/-/PDE mice (12 weeks) was less, compared with that in WT/PDE mice, p<0.05. The damage of the cartilage in HtrA1-/-;Col11a1+/- mice (15 months) was also less, compared with that in Col11a1+/- mice, p<0.05. Results from immunohistostaining indicated that the expression of Mmp-13 was decreased in the HtrA1-/-/PDE and HtrA1-/-;Col11a1+/- mice.
Conclusions: We conclude that the deletion of HtrA1 can significantly attenuate the progressive process of condylar cartilage degeneration. Thus, HTRA1 may be a potential target for the development of disease-modifying OA drugs.
AADR/CADR Annual Meeting
2018 AADR/CADR Annual Meeting (Fort Lauderdale, Florida)
Fort Lauderdale, Florida
2018
0040
Craniofacial Biology Research
  • Liu, Chenlu  ( Harvard School of Dental Medicine , Boston , Massachusetts , United States ;  Sichuan University , Chengdu , China )
  • Mian, Michelle  ( Harvard School of Dental Medicine , Boston , Massachusetts , United States )
  • Oka, Chio  ( Nara Institute of Science and Technology , Ikoma , Japan )
  • Xu, Lin  ( Harvard School of Dental Medicine , Boston , Massachusetts , United States ;  Harvard Medical School , Boston , Massachusetts , United States )
  • Li, Yefu  ( Harvard School of Dental Medicine , Boston , Massachusetts , United States ;  Harvard Medical School , Boston , Massachusetts , United States )
  • NONE
    Oral Session
    Temporomandibular Joint and Mandibular Condylar Cartilage
    Wednesday, 03/21/2018 , 01:30PM - 03:00PM