Intrinsic repair of full-thickness articular cartilage defects in the axolotl salamander

Objective: The ability to fully regenerate lost limbs has made the axolotl salamander (Ambystoma mexicanum) a valuable model for studies of tissue regeneration. The current experiments investigate the ability of these vertebrates to repair large articular cartilage defects and restore normal hyaline cartilage and joint structure independent of limb amputation. Methods: Full-thickness articular cartilage defects were made by resection of the medial femoral condyle to the level of the metaphysis. At 0, 2 days, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 weeks post-surgery, the repair process was analyzed on H&E and Safranin-O stained 7 μm tissue sections. Symmetric Kullback-Leibler (SKL) divergences were used to assess proteoglycan staining intensities. Immunohistochemistry was performed for collagen types I and II. Results: A fibrous " interzone-like" tissue occupies the intraarticular space of the axolotl femorotibial joint and no evidence of joint cavitation was observed. By 4 weeks post-surgery, cells within the defect site exhibited morphological similarities to those of the interzone-like tissue. At 24 weeks, joint structure and cartilaginous tissue repair were confirmed by immunohistochemistry for collagen types I and II. Quantitation of Safranin-O staining indicated restoration of proteoglycan content by 18 weeks. Conclusions: The axolotl femorotibial joint has morphological similarities to the developing mammalian diarthrodial joint. Cells in the intraarticular space may be homologous to the interzone tissue and contribute to intrinsic repair of full-thickness articular cartilage defects. Taken together, these results suggest that the axolotl may serve as a valuable model for the investigation of cellular and molecular mechanisms that achieve full articular cartilage repair.