Increased Production of Clusterin in Biopsies of Repair Tissue following Autologous Chondrocyte Implantation

Helen S. McCarthy*, Jos Malda, James B. Richardson, Sally Roberts

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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. Design. 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.

Original languageEnglish
Pages (from-to)227-238
Number of pages12
JournalCartilage
Volume4
Issue number3
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Funding

We are grateful to the Arthritis Research UK for supporting this work (Grants 19429 and 18480), to the Dutch Arthritis Foundation for supporting JM, to Dr. B.F. Murphy (Austin Health, Melbourne, Australia) for providing the G7 clusterin antibody and to The John Charnley Laboratory, RJAH Orthopaedic Hospital, UK, for the expansion and preparation of harvested chondrocytes used in the ACI procedures. The anti-collagen type II antibody (clone CIIC1) developed by Rikard Holmdahl and Kristofer Rubin was obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242.

Keywords

  • autologous chondrocyte implantation
  • clusterin
  • cartilage
  • repair

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