ArticleOsteoarthritis and cartilage2026
3D Light sheet microscopy reveals aging osteoarthritis-associated joint-innervated nerve remodeling in mouse knee joints.
Article in Osteoarthritis and cartilage, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesOsteoarthritis (OA) is a prevalent age related joint disease-causing chronic pain. This study investigated how nociceptive and sympathetic nerve innervation in the mouse knee joint changes with age and OA progression, and how these changes relate to pain and disease severity.
methodsThirty-eight mice were assigned to four groups: young male (M
resultsAged males exhibited the greatest OA severity and significantly lower PAM withdrawal thresholds compared with young males, indicating increased pain sensitivity with age. This phenotype was accompanied by marked remodeling of the total PGP9.5⁺ nerve network in the knee joint. Specifically, aged males showed approximately 2.0-fold greater total PGP9.5⁺ nerve fiber length and 3.6-fold higher PGP9.5⁺ branching complexity compared with young males. Nociceptive CGRP⁺ nerve fiber density was also elevated in aged males, whereas sympathetic TH⁺ fiber density remained unchanged across age and sex groups. Female mice exhibited no significant age-related differences in PAM withdrawal thresholds, cartilage degeneration (OARSI scores), or joint innervation. Consistent with joint-level findings, DRG analyses revealed ∼1.3-fold more CGRP⁺ neurons and ∼2.1-fold higher PIEZO2 expression in aged males compared with young males, while females showed no significant age-dependent changes.
conclusionEnhanced nociceptive but not sympathetic nerve remodeling in the anterior region of the knee is associated with increased OA severity and knee pain in the M
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