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Adamts5 (aggrecanase‐2) is widely expressed in the mouse musculoskeletal system and is induced in specific regions of knee joint explants by inflammatory cytokines
Author(s) -
Wylie James D.,
Ho Jason C.,
Singh Shweta,
McCulloch Daniel R.,
Apte Suneel S.
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21508
Subject(s) - aggrecanase , aggrecan , versican , furin , cartilage , extracellular matrix , proteoglycan , adamts , arthritis , pathology , osteoarthritis , chemistry , microbiology and biotechnology , medicine , immunology , metalloproteinase , anatomy , matrix metalloproteinase , articular cartilage , biology , biochemistry , enzyme , alternative medicine , thrombospondin
ADAMTS5 (aggrecanase‐2) is an extracellular matrix‐degrading protease implicated in cartilage destruction in arthritis. Our goals were to determine expression sites of Adamts5 in the murine musculoskeletal system and in an ex vivo joint inflammation model. In mice with an intragenic LacZ reporter controlled by the Adamts5 promoter, β‐galactosidase staining was used to identify Adamts5 expressing cells. Mice expressing one wild‐type Adamts5 allele were used to determine distribution of Adamts5 mRNA, cleaved aggrecan and versican, and the ADAMTS5 activating enzymes furin and PACE4. Quantitative RT‐PCR and immunoblotting were used to validate the immunohistochemistry results. Adamts5 was expressed in mouse synovium, tenosynovium, bone marrow sinusoids, tendons, ligaments, ligament insertions, periosteal cells, and bone vasculature. In knee joint explants treated with IL‐1α and TNFα, Adamts5 expression was induced in tenocytes, synovium, and in patellar, but not femoral or tibial articular cartilage. In contrast, increased proteoglycan breakdown in tibial and femoral articular cartilage was associated with increased immunohistochemical staining of PACE4 and furin. These studies identify diverse cell types in the musculoskeletal system that express Adamts5 . They also suggest that Adamts5 induction in joint components other than cartilage, and its post‐translational activation by PACE4 and/or furin may be important in the pathophysiology of arthritis. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:226–233, 2012