TY - JOUR
T1 - The chemokine receptor CCR5 plays a role in post-traumatic cartilage loss in mice, but does not affect synovium and bone
AU - Takebe, K.
AU - Rai, M. F.
AU - Schmidt, E. J.
AU - Sandell, L. J.
N1 - Publisher Copyright:
© 2014 Osteoarthritis Research Society International.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Objective: C-C chemokine receptor type 5 (CCR5) has been implicated in rheumatoid arthritis and several inflammatory diseases, where its blockade resulted in reduced joint destruction. However, its role in modulating cartilage and bone changes in post-traumatic osteoarthritis (OA) has not yet been investigated. In this study, we investigated changes in articular cartilage, synovium and bone in a post-traumatic OA model using CCR5-deficient (CCR5-/-) mice. Method: Destabilization of the medial meniscus (DMM) was performed on the right knee of 10-week old CCR5-/- and C57BL/6J wild-type (WT) mice to induce post-traumatic OA. The contralateral left knee served as sham-operated control. Knee joints were analyzed at 4-, 8- and 12-weeks after surgery to evaluate cartilage degeneration and synovitis by histology, and bone changes via micro-CT. Results: Our findings showed that CCR5-/- mice exhibited significantly less cartilage degeneration than WT mice at 8- and 12-weeks post-surgery. CCR5-/- mice showed some altered bone parameters 18- and 22-weeks of age, but body size and weight were not affected. The effect of CCR5-ablation was insignificant at all time points post-surgery for synovitis and for bone parameters such as bone volume/total volume, connectivity density index (CDI), structure model index (SMI), subchondral bone plate thickness, and trabecular bone number, thickness and spacing. Conclusion: These findings suggest that CCR5-/- mice developed less cartilage degeneration, which may indicate a potential protective role of CCR5-ablation in cartilage homeostasis. There were no differences in bone or synovial response to surgery suggesting that CCR5 functions primarily in cartilage during the development of post-traumatic OA.
AB - Objective: C-C chemokine receptor type 5 (CCR5) has been implicated in rheumatoid arthritis and several inflammatory diseases, where its blockade resulted in reduced joint destruction. However, its role in modulating cartilage and bone changes in post-traumatic osteoarthritis (OA) has not yet been investigated. In this study, we investigated changes in articular cartilage, synovium and bone in a post-traumatic OA model using CCR5-deficient (CCR5-/-) mice. Method: Destabilization of the medial meniscus (DMM) was performed on the right knee of 10-week old CCR5-/- and C57BL/6J wild-type (WT) mice to induce post-traumatic OA. The contralateral left knee served as sham-operated control. Knee joints were analyzed at 4-, 8- and 12-weeks after surgery to evaluate cartilage degeneration and synovitis by histology, and bone changes via micro-CT. Results: Our findings showed that CCR5-/- mice exhibited significantly less cartilage degeneration than WT mice at 8- and 12-weeks post-surgery. CCR5-/- mice showed some altered bone parameters 18- and 22-weeks of age, but body size and weight were not affected. The effect of CCR5-ablation was insignificant at all time points post-surgery for synovitis and for bone parameters such as bone volume/total volume, connectivity density index (CDI), structure model index (SMI), subchondral bone plate thickness, and trabecular bone number, thickness and spacing. Conclusion: These findings suggest that CCR5-/- mice developed less cartilage degeneration, which may indicate a potential protective role of CCR5-ablation in cartilage homeostasis. There were no differences in bone or synovial response to surgery suggesting that CCR5 functions primarily in cartilage during the development of post-traumatic OA.
KW - Bone
KW - CCR5
KW - Cartilage
KW - Osteoarthritis
KW - Post-traumatic
KW - Synovium
UR - http://www.scopus.com/inward/record.url?scp=84924931349&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2014.12.002
DO - 10.1016/j.joca.2014.12.002
M3 - Article
C2 - 25498590
AN - SCOPUS:84924931349
SN - 1063-4584
VL - 23
SP - 454
EP - 461
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 3
ER -