title: Increased Production of Clusterin in Biopsies of Repair Tissue following Autologous Chondrocyte Implantation.
abstract: OBJECTIVE
  To characterize the immunolocalization of clusterin in the repair cartilage of patients having undergone autologous chondrocyte implantation (ACI) and evaluate correlation to clinical outcome.
  
  
  METHODS
  Full-depth core biopsies of repair tissue were obtained from 38 patients who had undergone ACI at an average of 18 ± 13 months previously (range 8-67 months). The biopsies were snap frozen, cryosectioned, and clusterin production immunolocalized using a specific monoclonal clusterin antibody and compared with normal and osteoarthritic cartilage. Clinical outcome was assessed from patients preoperatively, at the time of biopsy, and annually postoperatively.
  
  
  RESULTS
  Intensity of immunostaining for clusterin decreased with age in healthy cartilage tissue. Clusterin was detected to a variable degree in 37 of the 38 ACI cartilage biopsies, in single and clustered chondrocytes, in the pericellular capsule and the cartilage extracellular matrix, as well as the osteocytes and osteoid within the bone. Chondrocytes in hyaline repair tissue were significantly more immunopositive than those in fibrocartilage repair tissue. Clinical outcome improved significantly post-ACI, but did not correlate with the presence of clusterin in the repair tissue.
  
  
  CONCLUSIONS
  These results demonstrate the presence of clusterin in actively repairing human cartilage and indicate a different distribution of clusterin in this tissue compared to normal cartilage. Variability in clusterin staining in the repair tissue could indicate different states of chondrogenic differentiation. The clinical significance of clusterin within repair tissue is difficult to assess, although the ideal functioning repair tissue morphology should resemble that of healthy adult cartilage.
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust and ISTM (Keele University), Oswestry, Shropshire, UK.
authors.forename: Helen S
authors.initials: HS
authors.lastname: McCarthy
authors.affiliation: Department of Orthopaedics, University Medical Centre, Utrecht, Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust and ISTM (Keele University), Oswestry, Shropshire, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Richardson
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust and ISTM (Keele University), Oswestry, Shropshire, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
keywords: autologous chondrocyte implantation; cartilage; clusterin; repair