title: The chemokine receptor CCR5 plays a role in post-traumatic cartilage loss in mice, but does not affect synovium and bone.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: takebek@wudosis.wustl.edu.
authors.forename: K
authors.initials: K
authors.lastname: Takebe
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: raim@wudosis.wustl.edu.
authors.forename: M F
authors.initials: MF
authors.lastname: Rai
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: schmidtej@wudosis.wustl.edu.
authors.forename: E J
authors.initials: EJ
authors.lastname: Schmidt
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: sandelll@wudosis.wustl.edu.
authors.forename: L J
authors.initials: LJ
authors.lastname: Sandell
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging* / Q000473:pathology; D007718:Knee Injuries / Q000150:complications; D051379:Mice; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D013583:Synovial Membrane / Q000473:pathology*; D013977:Tibia / Q000000981:diagnostic imaging* / Q000473:pathology; D000070600:Tibial Meniscus Injuries; D055114:X-Ray Microtomography
chemical_list: C000592874:CCR5 protein, mouse; D019713:Receptors, CCR5
keywords: Bone; CCR5; Cartilage; Osteoarthritis; Post-traumatic; Synovium