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The Role of HA and Has2 in the Development and Function of the Skeleton

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Book cover Extracellular Matrix in Development

Part of the book series: Biology of Extracellular Matrix ((BEM))

Abstract

Hyaluronan (HA) is present throughout the body, including all the bones and cartilages of the skeleton, where it may fulfill both a structural and metabolic role depending on its molecular size. In mammals, HA is produced by three hyaluronan synthases (Has), of which Has2 is the predominant form in cartilage and bone. HA can be degraded by hyaluronidases (Hyal) and free radicals. Mammals possess five hyaluronidases, of which Hyal1 and Hyal2 are thought to be predominant in cartilage and bone. The structural role of HA in cartilage is dependent on its ability to form proteoglycan aggregates, whereas its metabolic role involves intracellular signaling induced by interaction with receptors such as CD44 and RHAMM. Such signaling differs between high-molecular-weight HA and its fragments. HA and its fragments play a major role in endochondral bone formation and possibly intramembranous bone formation, as they can regulate the differentiation and action of chondrocytes, osteoblasts, and osteoclasts. Cartilage-specific depletion of HA synthesis has been studied in floxed Has2 mice that have been crossed with mice expressing Cre under control of either the Prx1 or the Col2a1 promoter. Such deletion of Has2 gene expression results in a chondrodysplastic phenotype, in which all endochondral bones of the skeleton are severely truncated. The phenotype is characterized by severely impaired longitudinal growth of the bones due to abnormal organization and differentiation within the growth plates, particularly in the process of chondrocyte hypertrophy. The Col2a1-driven mice also exhibit defective modeling of the endochondral bone.

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  1. Genetics Unit, Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, QC, H3G 1A6, Canada

    Peter J. Roughley & Pierre Moffatt

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  1. Peter J. Roughley
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  2. Pierre Moffatt
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Correspondence to Peter J. Roughley .

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  1. School of Medicine, Department of Cell Biology, University of Virginia, Jeanette Lancaster Way 200, Charlottesville, 22903, Virginia, USA

    Douglas W. DeSimone

  2. School of Medicine, Dept. Cell Biology & Physiology, Washington University, South Euclid Avenue 660, St. Louis, 63110, Missouri, USA

    Robert P. Mecham

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Roughley, P.J., Moffatt, P. (2013). The Role of HA and Has2 in the Development and Function of the Skeleton. In: DeSimone, D., Mecham, R. (eds) Extracellular Matrix in Development. Biology of Extracellular Matrix. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-35935-4_9

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