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

Abstract

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. Developmental Dynamics 240:404-412,

Cx43-Dependent Skeletal Phenotypes Are Mediated by Interactions between the Hapln1a-ECM and Sema3d during Fin Regeneration

“…However, of the three enzymes, HAS2 is uniquely essential for life and neither Has1 nor Has3 compensate for the loss of HAS2 [ 42 ]. Conditional HAS2 gene knockout in mice causes shortened axial and appendicular skeleton and defects in patterning of digits [ 50 , 65 ], and strikingly, overexpression of Has2 in the developing chick limb bud mesoderm also leads to shortened bones with abnormal morphology and positioning [ 56 ]. Together, these findings suggest a critical need for regulating HA metabolism and highlight the significance of HA produced by Has2.…”

Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

“…More recent analyses, however, have shown that HA is a multifunctional molecule for which a number of key roles have already been identified during and following development. These inter- and intracellular functions include roles in cell migration, tumour invasion, and cellular response to injury (e.g., [ 5 – 10 ]).…”

The control and importance of hyaluronan synthase expression in palatogenesis

“…Unlike other glycosaminoglycans (GAGs), HA is not synthesized within the Golgi apparatus, but at the plasma membrane by the addition of UDP-Glucuronic acid and UDP-N-acetyl glucosamine on membrane bound enzymes known as HA synthases (Has) (Moffatt et al, 2011). These enzymes synthesize HA and secrete it directly through the plasma membrane into the extracellular environment (Moffatt et al, 2011).…”

“…Unlike other glycosaminoglycans (GAGs), HA is not synthesized within the Golgi apparatus, but at the plasma membrane by the addition of UDP-Glucuronic acid and UDP-N-acetyl glucosamine on membrane bound enzymes known as HA synthases (Has) (Moffatt et al, 2011). These enzymes synthesize HA and secrete it directly through the plasma membrane into the extracellular environment (Moffatt et al, 2011). The Has family is comprised of three members; Has1, Has2, and Has3, which are all composed of a transmembrane domain and a large cytosolic catalytic domain (Laurent and Fraser, 1992; Weigel et al, 1997; Moffatt et al, 2011).…”

“…These enzymes synthesize HA and secrete it directly through the plasma membrane into the extracellular environment (Moffatt et al, 2011). The Has family is comprised of three members; Has1, Has2, and Has3, which are all composed of a transmembrane domain and a large cytosolic catalytic domain (Laurent and Fraser, 1992; Weigel et al, 1997; Moffatt et al, 2011). However, they differ in their stability, in the time they are expressed during development (Tien and Spicer, 2005), their level of expression in different cell types, with growing cells expressing higher levels than those that are not (Jacobson et al, 2000) and the way they are affected by external stimuli (Ellis et al, 2007).…”