Objective: To investigate the therapeutic effects of basic fibroblast growth factor (bFGF) contained in gelatin hydrogel microspheres on osteoarthritis (OA) development in rabbit knee joints.Methods: ¹²⁵I‐labeled bFGF contained in gelatin hydrogel microspheres was administered to the knee joints of normal rabbits to confirm the sustained‐release kinetics of bFGF in the knee joint. In addition, the expression of proteoglycan core protein messenger RNA was examined using real‐time polymerase chain reaction to confirm the anabolic effects on the cartilage treated with the sustained release of bFGF. The bFGF in gelatin hydrogel microspheres was administered to the knee joint once every 3 weeks (a total of twice) from 4 weeks after anterior cruciate ligament transection (ACLT). Ten weeks after ACLT, gross morphologic and histologic examinations were performed.Results: Sustained release of bFGF in the knee joint continued for >7 days and induced the anabolic effects on the cartilage. Intraarticular injections of bFGF contained in gelatin hydrogel microspheres suppressed the progression of OA in the ACLT rabbit model.Conclusion: Our findings demonstrated that sustained release of bFGF into the joint had therapeutic effects on OA development in a rabbit model. Our results suggest the potential feasibility of a new conservative treatment for OA.

The purpose of this study was to investigate the influence of hydrostatic pressure (HP) on apoptosis and expression of heat‐shock protein 70 (HSP70) in chondrocytes cultured in alginate beads. Chondrocytes were isolated from the articular cartilage of rabbit joints and seeded in alginate beads. The beads in Group A were cultured for less than 24 h after being embedded with the chondrocytes, while those in Group B were cultured for 2 weeks. Both groups were exposed to HP of 10 or 50 MPa for 12 or 24 h. The beads in Groups A and B that were not exposed to HP were regarded as controls. Apoptotic cells induced by exposure to HP were quantified using the TUNEL method. Immunohistochemical analysis for HSP70 and in situ TUNEL analysis were also performed. Apoptotic chondrocytes were not observed in the control cells under atmospheric pressure, whereas apoptosis was observed in the beads in Group A, and the number of apoptotic cells increased as the duration and magnitude of HP increased. On the other hand, we observed no significant population of apoptotic cells in the beads in Group B. Chondrocytes expressing HSP70 were not TUNEL positive in the histological analysis. Excessively strong HP could evoke apoptosis when the extracellular matrix did not accumulate around the chondrocytes. HSP70 expression was related to occurrence of apoptosis that resulted from HP. These findings suggest a mechanism for the pathogenesis of cartilage degeneration in osteoarthritis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

The objective of this study was to investigate the effects of heat stimulation on the expression of extracellular matrix genes and heat‐shock protein 70 (HSP70) in rabbit articular cartilage in vivo. Heat stimulation was applied to the knee joints of Japanese white rabbits for 20 min using a microwave (MW) applicator (2.45‐GHz, 0–80 W). After 8–72 h, the articular cartilage was removed from the knee joints and proteins and total RNA were extracted. As controls, knee joints without heat stimulation were analyzed. The expression of HSP70 was confirmed by real‐time PCR and Western blotting. The expression of proteoglycan core protein (PG) and type II collagen (Col II) was quantified using real‐time PCR to assess cartilage matrix metabolism. Compared to controls, HSP70 expression was higher with more than 40 W of heat stimulation. The expression of PG and Col II mRNA was higher, with more than 20 W of heat stimulation and peaked with 40 W. When quercetin was used to inhibit the induction of HSP70 expression, PG mRNA expression did not increase. External MW application stimulated HSP70 expression in the articular cartilage in vivo. The expression of extracellular matrix genes was increased by appropriate heat stimulation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:34–41, 2008