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Osteoarthritis Cartilage. 2011 Jul;19(7):886-94. doi: 10.1016/j.joca.2011.04.007. Epub 2011 Apr 23.

Cartilaginous repair of full-thickness articular cartilage defects is induced by the intermittent activation of PTH/PTHrP signaling.

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1
Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Abstract

OBJECTIVE:

We studied the effects of the transient activation of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling during the repair of 5-mm-diameter full-thickness defects of articular cartilage in the rabbit.

MATERIALS AND METHODS:

Cylindrical full-thickness articular cartilage defects of 5mm in diameter were artificially created in the femoral trochlea of male adolescent Japanese white rabbits using a hand-drill. Recombinant human PTH(1-84) was then administered into the joint cavity continuously or intermittently for 2 weeks post-injury. The reparative tissues were histologically examined at 2, 4, and 8 weeks, and were also immunohistochemically examined for type II collagen. Double immunostaining analysis was also performed for the PTH/PTHrP receptor and proliferating cell nuclear antigen (PCNA) in the regenerating tissues.

RESULTS:

No evidence of cartilage formation was evident throughout the period of the experiments in injured animals administered saline alone. In contrast, cartilage formation occurred at 4 weeks in both the continuous and intermittent PTH-treated defects. At 8 weeks post-injury, for the intermittently treated defects, the regenerated cartilage successfully resurfaced the defects and the original bone-articular cartilage junction was recovered. In contrast, the defects were covered with fibrous or fibrocartilaginous tissues in the continuously administered group. PCNA and PTH/PTHrP receptor-double positive mesenchymal cells were significantly increased in both the continuous and intermittent PTH-treated defects at 2 weeks post-injury.

CONCLUSIONS:

The present results suggest that the transient activation and release from PTH/PTHrP signaling during the early stages of the cartilage repair process facilitates the induction of regenerative chondrogenesis in full-thickness articular cartilage defects.

PMID:
21571083
DOI:
10.1016/j.joca.2011.04.007
[Indexed for MEDLINE]
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