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Am J Pathol. 2019 Jul;189(7):1423-1434. doi: 10.1016/j.ajpath.2019.03.013. Epub 2019 Apr 30.

High-Temperature Requirement A1 Protease as a Rate-Limiting Factor in the Development of Osteoarthritis.

Author information

1
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
2
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
3
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
4
Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, Japan.
5
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: yefu_li@hms.harvard.edu.
6
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: lin_xu@hms.harvard.edu.

Abstract

Preserving the mature articular cartilage of joints is a critical focus in the prevention and treatment of osteoarthritis. We determined whether the genetic inactivation of high-temperature requirement A1 (HtrA1) can significantly attenuate the degradation of articular or condylar cartilage. Two types of mouse models of osteoarthritis were used, a spontaneous mutant mouse model [type XI collagen-haploinsufficient (Col11a1+/-) mice] and two post-traumatic mouse models [destabilization of the medial meniscus (DMM) on the knee and a partial discectomy (PDE) on the temporomandibular joint]. Three different groups of mice were generated: i) HtrA1 was genetically deleted from Col11a1+/- mice (HtrA1-/-;Col11a1+/-), ii) HtrA1-deficient mice (HtrA1-/-) were subjected to DMM, and iii) HtrA1-/- mice were subjected to PDE. Knee and temporomandibular joints from the mice were characterized for evidence of cartilage degeneration. The degradation of articular or condylar cartilage was significantly delayed in HtrA1-/-;Col11a1+/- mice and HtrA1-/- mice after DMM or PDE. The amount of collagen type VI was significantly higher in the articular cartilage in HtrA1-/-;Col11a1+/- mice, compared with that in Col11a1+/- mice. The genetic removal of HtrA1 may delay the degradation of articular or condylar cartilage in mice.

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