Altered localisation of transforming growth factor-beta 3 during endochondral ossification in rachitic chicks

Growth plates from chicks displaying hypocalcaemic rickets, hypophosphataemic rickets and dyschondroplasia were studied. Immunohistochemical staining using specific TGF-beta 3 antibodies showed disruption of TGF-beta 3 localisation in all three disorders. In hypocalcaemic rickets, transitional and hypertrophic chondrocytes showed expression of TGF-beta 3, while accumulating, proliferative chondrocytes showed little expression. In the accumulating hypertrophic chondrocytes of hypophosphataemic rickets there was a reduction in the number of chondrocytes expressing TGF-beta 3, but transitional cells stained intensely. In the accumulating transitional chondrocytes of dyschondroplastic physes there was a reduction in the number of chondrocytes containing TGF-beta 3 and, in addition, the concentration of TGF-beta 3 appeared reduced. In all three disorders, there was localisation of some TGF-beta 3 in chondrocytes that appeared to be differentiating within the areas of repair. In addition, little TGF-beta 3 was detected in osteoclasts resorbing accumulated matrix from hypocalcaemic, hypophosphataemic and dyschondroplastic growth plates. These in vivo studies show a reduction in TGF-beta 3 localisation within growth plate chondrocytes and osteoclasts in three disorders in which chondrocytes cease to differentiate. This suggests that TGF-beta 3 may be important during chondrocyte differentiation in the growth plate.