Matrix remodeling and chondrocyte hypertrophy. (A-D) Sections of the tibial articular cartilage of 6-week-old (A, C) and 12-week-old (B, D) normal Mig-6-flox knees stained with Safranin-O (A, B) or immunostained for NITEGE-positive aggrecan-cleavage fragments (NITEGE, C, D). The normal articular cartilage stains uniformly for Safranin-O, and aggrecan cleavage fragments are not detected. (E-H) Sections of the tibial articular cartilage of 6-week-old (E, G) and 12-week-old (F, H) Mig-6-flox;Prx1Cre (Mig-6-cko) knees stained with Safranin-O (E, F) or immunostained for NITEGE-positive aggrecan-cleavage fragments (NITEGE, G, H). The superficial zone of Mig-6-cko knee articular cartilage stains weakly for Safranin-O (* in E, F) and contains NITEGE-positive aggrecan cleavage fragments (arrows in G, H) which are more abundant at 12 weeks than at 6 weeks (compare H to G). (I-L) Sections of the tibial articular cartilage (I, J) of six-week-old normal Mig-6-flox (I) and Mig-6-flox-cko (J) knees, immunostained with a collagen type × antibody to identify hypertrophic chondrocytes. Only an occasional hypertrophic chondrocyte is detected in either normal or Mig-6-cko articular cartilage at six weeks of age (arrows in I, J). As a positive control (K, L) note the robust collagen type × immunostaining in the hypertrophic chondrocytes of both normal Mig-6-flox (K) and Mig-6-cko growth plates (arrowheads in K, L). (M-P) Sections of the tibial articular cartilage of 12-week-old normal Mig-6-flox (M, N) and Mig-6-flox-cko (O, P) knees, immunostained with a collegen type × antibody (M, O) or subjected to in situ hybridization for type × collagen mRNA (N, P). While few or no hypertrophic chondrocytes are detected in normal articular cartilage, several hypertrophic chondrocytes are observed in Mig-6-cko articular cartilage (arrows in O, P). Scale Bar = 50 μm (A-H); 20 μm (I-P).
Shepard et al. Arthritis Research & Therapy 2013 15:R60 doi:10.1186/ar4233