Detalle Publicación

CC-Chemokine receptor-2 expression in osteoblasts contributes to cartilage and bone damage during post-traumatic osteoarthritis

Autores: Willcockson, H.; Ozkan, H.; Valdés Fernández, José; Arbeeva, L.; Mucahit, E.; Musawwir, L.; Hooper, L. B.; Granero Molto, Froilan; Prosper Cardoso, Felipe; Longobardi, L. (Autor de correspondencia)
Título de la revista: BIOMOLECULES
ISSN: 2218-273X
Volumen: 13
Número: 6
Páginas: 891
Fecha de publicación: 2023
Resumen:
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 Ccr2 osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible Ccr2 inactivation in Collagen1 & alpha;-expressing cells to obtain osteoblasts lacking Ccr2 (CCR2-Col1 & alpha;KO). We stimulated PTOA changes in CCR2-Col1 & alpha;KO and CCR2+/+ 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-Ccr2 inactivation delayed articular cartilage damage and matrix degeneration compared to CCR2+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1 & alpha;-Ccr2 deletion led to less evident improvements. Osteoblast-Ccr2 deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that Ccr2 expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues.