Expression of the PTH/PTHrP receptor in chondrogenic cells during the repair of full-thickness defects of articular cartilage

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Objective: We studied the accumulation of parathyroid hormone (PTH)/PTHrP receptor-positive mesenchymal cells using double immunohistochemistry and examined whether this correlated with the subsequent regeneration of 3-mm-diameter full-thickness defects of articular cartilage. Materials and methods: Cylindrical full-thickness articular cartilage defects (3 mm) were artificially created in the femoral trochlea of male adolescent Japanese white rabbits (n = 210) with a hand-drill. Recombinant human PTH(1-84) was then administered into the defect cavities with an osmotic pump for either 2 or 4 weeks post-injury. Following PTH treatment, the repair processes in the cartilage defects were histologically examined. Double immunostaining analyses for the PTH/PTH-related peptide (PTHrP) receptor and proliferating cell nuclear antigen (PCNA) in the regenerating tissues were then performed. Results: Activation of PTH/PTHrP receptor signaling by hPTH(1-84) results in the inhibition of chondrogenic differentiation in full-thickness articular cartilage defects. At the conclusion of the 2-week PTH treatment, the defect cavities were filled with undifferentiated mesenchymal cells, which were similar to the controls. In addition, almost all of these cells localized at the center of the injuries were both PTH/PTHrP receptor- and PCNA-positive. In contrast, after prolonged PTH treatment for 4 weeks, there was no indication of a cartilaginous repair response and cells that had migrated to the defect cavities were found to have irreversibly lost expression of the PTH/PTHrP receptor. Conclusions: The chondrogenic capacity of cells that had migrated to the area of these defect cavities is closely associated with their ability to express the PTH/PTHrP receptor. Moreover, these cells maintain their chondrogenic potential within only a limited time-span of 2 weeks. © 2006 OsteoArthritis Research Society International.




Mizuta, H., Kudo, S., Nakamura, E., Takagi, K., & Hiraki, Y. (2006). Expression of the PTH/PTHrP receptor in chondrogenic cells during the repair of full-thickness defects of articular cartilage. Osteoarthritis and Cartilage, 14(9), 944–952.

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