title: Cartilaginous repair of full-thickness articular cartilage defects is induced by the intermittent activation of PTH/PTHrP signaling.
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.
  
  
  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.
authors.affiliation: Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kudo
authors.forename: H
authors.initials: H
authors.lastname: Mizuta
authors.forename: K
authors.initials: K
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D005269:Femur; D007150:Immunohistochemistry; D008297:Male; D008648:Mesoderm / Q000166:cytology; D010281:Parathyroid Hormone / Q000378:metabolism / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D010281:Parathyroid Hormone; D018809:Proliferating Cell Nuclear Antigen; D044168:Receptor, Parathyroid Hormone, Type 1