PMC:523229 / 31234-34443 JSONTXT

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Instead, increased expression of Col10a1 was seen in a zone of largely LACZ-negative cells stretching from the cartilage adjacent to the ossification front (where Col10a1 is normally expressed in maturing cartilage cells), toward the regions where surface articular cartilage was severely eroded or missing (Figure 6A and 6B, arrowheads). Previous studies suggest that parathyroid hormone-related protein, a diffusible signal made in the articular surface, may normally inhibit maturation of underlying cartilage (Vortkamp et al. 1996; Weir et al. 1996). Local loss of the articular surface could remove this inhibition and lead to a cell-nonautonomous acceleration of maturation in chondrocytes underlying points of articular erosion.\nFigure 6 Synovial Membrane Expansion, Articular Surface Erosion, and Accelerated Maturation of Underlying Cartilage in Ankles of Bmpr1a Mutant Mice\nNear adjacent sections from the tarsal 2-metatarsal II joint of 7-d-old mice. (A and B) LACZ staining (blue) shows Cre-mediated recombination is largely restricted to articular (arrowheads) and synovial cells (asterisks) in both controls and mutants. (C and D) In situ hybridization shows Col10 expression expands in mutants toward regions of synovial membrane expansion and articular surface erosion (brackets and arrows). This may be a cell nonautonomous effect of joint damage, since the LACZ expressing cells at the articular surface do not show upregulation of Col10 (arrowheads) and the region of expanded Col10 expression is largely made up of cells that have not undergone Cre-mediated recombination. Note the formation of a cartilaginous bridge along the joint capsule of the mutant where joint formation is disrupted at earlier stages (B, white arrowhead, and Figure 3, white arrowheads). (A) Scale bar = 75 μm. This synovial hypertrophy is associated with increased numbers of mononuclear cells resembling synoviocytes or macrophages, cell types that are difficult to distinguish even with surface markers at early postnatal stages. However, no neutrophils were observed, suggesting that there is little inflammation. At later stages synovial hypertrophy is reduced. Further work will be needed to determine whether synovial development is regulated by BMP signaling, or whether the synovium becomes enlarged as a response to nearby skeletal malformations (such as fusion of the second and central tarsals or defects in the articular 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