Loss of Bmpr1a Signaling Leads to Articular Cartilage Fibrillation and Degeneration in Digits and Knees of Aging Mice
(A–D) Near adjacent sections of metatarsal-phalangeal joints from 9 month old mice. Articular cartilage of controls is complete and stains strongly with Safranin O (A, orange stain). In contrast, articular cells of mutants are severely fibrillated or absent with much reduced staining of Safranin O (C, arrowheads). LACZ expression confirms Cre-mediated recombination has occurred in articular cells (B and D).
(E–P) Sagittal sections through knee joints of 7-wk- (E–J) or 9-mo-old animals (K–P); fe, femur; ti, tibia; gp, growth plate. Seven weeks after birth, the height of the tibial epiphysis is reduced in mutants (E and H, bars), and their articular layer stains poorly with Safranin O, is fibrillated, and is strikingly thinner (F and I, black arrowhead, and brackets). Near adjacent sections with LACZ staining confirm Cre-mediated recombination has occurred in articular cells (G and J). Note that in mutants, LACZ is absent in cells adjacent to those that do stain with Safranin O, suggesting Bmpr1a may act cell autonomously (I and J, white arrowheads). At 9 mo old, the mutant tibial epiphysis is extremely thin (K and N, bars), and the articular layer is completely absent, leaving bone to rub directly on bone (L and O, bracket). LACZ staining shows Cre-mediated recombination occurred in articular cells of controls (M) and in some remaining skeletal tissue of mutants (P). Also note aberrantly formed meniscal cartilage in mutants (E, H, K, and N, arrows), and increased sclerosis in mutant epiphyses (E, H, K, and N, asterisks).
(A and K) Scale bar = 50 μm; (I) scale bar = 300 μm.