Hyaluronan production by means of Has2 gene expression in chondrocytes is essential for long bone development.

Mice possessing no Has2 expression in chondrocytes died near birth and displayed abnormalities throughout their skeleton. By embryonic day 18.5, the long bones were short and wide, and possessed excessive mineralization within their diaphysis, with little evidence of diaphyseal bone modeling. However, this does not appear to be associated with an absence of blood vessel invasion or the reduced presence of osteoclasts. There was no evidence for the formation of an organized growth plate between the epiphysis and diaphysis, and while hypertrophic chondrocytes were present in this region they were abnormal in both appearance and organization. There was also increased cellularity in the epiphyseal cartilage and a corresponding decrease in the abundance of extracellular matrix, but aggrecan was still present. Thus, hyaluronan production by chondrocytes is not only essential for formation of an organized growth plate and subsequent long bone growth but also for normal modeling of the diaphyseal bone.