Hyaluronan is essential for the expansion of the cranial base growth plates

Exquisite control of chondrocyte function in the zone of hypertrophy result s in expansive growth of cartilaginous growth plates, and is a prerequisite for normal skeletal lengthening. We hypothesize that hyaluronan-mediated h ydrostatic pressure causes lacunae expansion in the zone of hypertrophy; an important mechanism in cartilaginous growth plate and associated skeletal expansion. The role of hyaluronan and CD44 in this mechanism was studied us ing organ culture of the bipolar cranial base synchondroses. Hyaluronan was present in the hypertrophic zones, pericellular to the hypertrophic chondr ocytes, while no hyaluronan was detected in the resting, proliferating and maturing zones. This localization of hyaluronan was associated with increas ed lacunae size, suggesting that chondrocytes deposit and retain pericellul ar hyaluronan as they mature. In comparison, Toluidine Blue staining was as sociated with the territorial matrix. Hyaluronidase, the hyaluronan-degradi ng enzyme, and CD44, the receptor for hyaluronan which also participates in the uptake and degradation of hyaluronan, were co-localized within the zon e of ossification. This pattern of expression suggests that cells in the ea rly zone of ossification internalize and degrade hyaluronan through a CD44- mediated mechanism. Treatment of the cultured segments with either Streptom yces hyaluronidase or hyaluronan hexasaccharides inhibited lacunae expansio n. These observations demonstrate that hyaluronan-mediated mechanisms play an important role in controlling normal skeletal lengthening.