Pannexin 3 deletion in mice results in knee osteoarthritis and intervertebral disc degeneration after forced treadmill running.

Autor: Wakefield B; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada., Tang J; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada., Hutchinson JL; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada.; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada., Kanji R; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada., Brooks C; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada., Grol MW; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada.; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada., Séguin CA; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada.; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada., Penuela S; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada., Beier F; Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, Ontario, Canada.; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2024 Aug; Vol. 42 (8), pp. 1696-1709. Date of Electronic Publication: 2024 Mar 18.
DOI: 10.1002/jor.25830
Abstrakt: Pannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggests Panx3 plays contrasting roles in traumatic versus aging osteoarthritis (OA) and intervertebral disc degeneration (IDD). However, whether its deletion influences the response of joint tissue to forced use is unknown. The purpose of this study was to determine if Panx3 deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and Panx3 knockout (KO) mice were randomized to either a no-exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage and IVD histopathology were evaluated by histology, while tibial secondary ossification centers were analyzed using microcomputed tomography (µCT). Both male and female Panx3 KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared with SED WT mice. Additionally, Panx3 KO mice developed reduced bone volume, and female PANX3 KO mice had lengthening of the lateral tubercle at the intercondylar eminence. In the lower lumbar spine, both male and female Panx3 KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deleting Panx3 and forced treadmill running induces OA and causes histopathological changes associated with the degeneration of the IVDs in mice.
(© 2024 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)
Databáze: MEDLINE
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