Active proliferation of mesenchymal cells prior to the chondrogenic repair response in rabbit full-thickness defects of articular cartilage

Osteoarthritis and Cartilage
Hiroshi MizutaYuji Hiraki

Abstract

In full-thickness articular defects, fibroblast growth factor-2 (FGF-2) participates in the chondrogenic repair response which occurs in a defect-size dependent manner. Here we demonstrate that FGF-2 plays a critical role in the proliferation of pre-chondrogenic mesenchymal cells during chondrogenic induction. Three-millimeter- or 5-mm-diameter cylindrical defects were created in the femoral trochlea of the rabbit knee. The defects received sterile saline or FGF-2 (50 pg/h) via an osmotic pump for the initial 2 weeks. We assessed the proliferative capacity of undifferentiated mesenchymal cells in the reparative tissue with the anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Using a total of 180 rabbits, we performed three sets of experiments. In the 3-mm-diameter defects, undifferentiated mesenchymal cells spontaneously initiated chondrogenic differentiation within 2 weeks, resulting in the regeneration of surfacing articular cartilage concomitantly with the repair of subchondral bone. No evidence of chondrogenesis was seen in the 5-mm-diameter defects, whereas application of FGF-2 promoted successful regeneration of articular cartilage. In the 3-mm-diameter defects and in the FGF-2-treated 5-mm defects, PCN...Continue Reading

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