| Summary: | In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether <i>Ccr2</i> osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible <i>Ccr2</i> inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking <i>Ccr2</i> (<i>CCR2</i>-<i>Col1αKO</i>). We stimulated PTOA changes in <i>CCR2</i>-<i>Col1αKO</i> and <i>CCR2</i>+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-<i>Ccr2</i> inactivation delayed articular cartilage damage and matrix degeneration compared to <i>CCR2</i>+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α-<i>Ccr2</i> deletion led to less evident improvements. Osteoblast-<i>Ccr2</i> deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that <i>Ccr2</i> expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues.
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