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 - Funding Information:
This study was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grants R01-AR050847 (Sandell, PI) and R01-AR045550 (Sandell, PI). Drs Rai and Schmidt were supported by Ruth L Kirschstein National Research Service Award Fellowship from National Institute of Arthritis and Musculoskeletal and Skin Diseases through grant T32-AR060719. Dr Rai is currently supported by NIH Pathway to Independence Award ( 1K99AR064837 ). Histology and micro-CT were available through the Washington University Musculoskeletal Research Center grant P30-AR057235 (Sandell, PI). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the National Institutes of Health.
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
VL - 23
SP - 454
EP - 461
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
SN - 1063-4584
IS - 3
ER -