title: Adamts5 (aggrecanase-2) is widely expressed in the mouse musculoskeletal system and is induced in specific regions of knee joint explants by inflammatory cytokines.
abstract: 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.
authors.affiliation: Cleveland Clinic, Department of Biomedical Engineering, Cleveland, Ohio 44195, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Wylie
authors.forename: Jason C
authors.initials: JC
authors.lastname: Ho
authors.forename: Shweta
authors.initials: S
authors.lastname: Singh
authors.forename: Daniel R
authors.initials: DR
authors.lastname: McCulloch
authors.forename: Suneel S
authors.initials: SS
authors.lastname: Apte
mesh_terms: D051722:ADAM Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000071116:ADAMTS5 Protein; D000818:Animals; D001168:Arthritis / Q000209:etiology*; D001842:Bone and Bones / Q000737:chemistry*; D045683:Furin / Q000032:analysis / Q000502:physiology; D007150:Immunohistochemistry; D053582:Interleukin-1alpha / Q000494:pharmacology*; D007719:Knee Joint / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043484:Proprotein Convertases / Q000032:analysis / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D053582:Interleukin-1alpha; D011509:Proteoglycans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C513086:Pcsk6 protein, mouse; D043484:Proprotein Convertases; D045683:Furin; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse