title: Analyses of early events during chondrogenic repair in rat full-thickness articular cartilage defects.
abstract: In this study we investigated the cellular events that occur during the onset of chondrogenic differentiation during the repair of full-thickness defects of articular cartilage. The V-shaped full-thickness cartilage defects (width 0.7 or 1.5 mm; depth 0.8 mm; length 4 mm) were created in the femoral patellar groove of rats using a custom-built twin-blade device. The time course of the repair response in these cartilage defects was examined using a semi-quantitative histological grading scale. Cartilaginous repair responses failed to occur in the larger 1.5 mm defects, which was covered only by fibrous scar tissue. In contrast, hyaline-like articular cartilage was regenerated concomitantly with the repair of the subchondral bone by 4 weeks in smaller 0.7 mm width defects. Cells in the reparative regions were then characterized by immunohistochemistry and in situ hybridization. Undifferentiated mesenchymal cells migrate into the defects and fill the cavities within 4 days of their creation. The expression of PCNA, N-cadherin, and PTH/PTHrP receptors was induced in cells at the center of the defects, where type II collagen-positive polygonal-shaped cells also begin to appear at day 7. Marrow-derived mesenchymal cells acquire higher levels of proliferative activity in induced cartilage cavities after their initial migration and filling of the smaller 0.7 mm defects. During the regenerative repair of articular cartilage in the rat, there is a distinctive step that appears to be analogous to the precartilaginous condensation that is pivotal during chondrogenesis in development.
authors.affiliation: Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Anraku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuta
authors.forename: Akira
authors.initials: A
authors.lastname: Sei
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kudo
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakamura
authors.forename: Kei
authors.initials: K
authors.lastname: Senba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology*; D020219:Chondrogenesis / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D053674:Aggrecans; D015820:Cadherins; D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D010281:Parathyroid Hormone; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; C493717:Runx2 protein, rat; D055758:SOX9 Transcription Factor