title: Heat-shock proteins and their role in chondrocyte protection, an application for autologous transplantation.
abstract: Articular cartilage injury presents a unique therapeutic challenge. As cartilage possesses no blood or nerve supply of its own it has a particular susceptibility to early injury and a poor capacity for self-repair. Treatment options are limited and injury can eventually lead to osteoarthritis. Autologous chondrocyte transplantation is an exciting therapeutic development, but despite initial encouraging results, graft failure and formation of fibro- as opposed to hyaline cartilage remain problematic. Bleeding is an inevitable consequence of surgery, and blood-induced cartilage damage is well documented. It is hypothesised here that protecting chondrocytes against blood could significantly improve results. Heat-shock protein induction may confer chondroprotection. The expression of heat-shock proteins in human chondrocytes and rat femoral head cartilage following heat shock was analysed by Western blotting, and red-blood-cell-induced chondrocyte death was assessed by cell viability and apoptosis by flow cytometry. We demonstrate that heat-shock induced expression of heat-shock protein 70 (HSP70) (rat and human) and HSP32 (human). Blood and blood products reduced rat cartilage proteoglycan synthesis and human chondrocyte viability, and induced human chondrocyte apoptosis at concentrations considerably lower than those reported previously. The induction of HSP70 in rat cartilage was ineffective in reducing chondrocyte death in the absence or presence of red blood cells or red cell products. Heat shock to human chondrocytes reduced low levels of apoptosis (<20%) and cell death induced by low levels of blood products, but not higher levels. Induction of HSP32 with diacetylrhein appeared to be more effective and may hold greater promise. Blood has potent adverse effects on chondrocytes and the induction and chondroprotective effects of heat-shock proteins could be applied to increase the initial success of implanted chondrocytes improving the outcome of autologous chondrocyte transplantation.
authors.affiliation: Experimental Pathology Group, William Harvey Research Institute, Saint Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Sawatzky
authors.forename: R
authors.initials: R
authors.lastname: Foster
authors.forename: M P
authors.initials: MP
authors.lastname: Seed
authors.forename: D A
authors.initials: DA
authors.lastname: Willoughby
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005270:Femur Head / Q000166:cytology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism* / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology; D006461:Hemolysis; D006801:Humans; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D014182:Transplantation, Autologous; D015854:Up-Regulation
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D018840:HSP70 Heat-Shock Proteins; D006454:Hemoglobins; D011509:Proteoglycans; C025292:diacerein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1