Hyaluronan synthesis and degradation in cartilage and bone |
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Authors: | E R Bastow S Byers S B Golub C E Clarkin A A Pitsillides A J Fosang |
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Institution: | (1) Arthritis Research Group, University of Melbourne Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, 3052, Victoria, Australia;(2) Matrix Biology Unit, Department of Genetic Medicine, Children, Youth and Women’s Health Services, North Adelaide, 5006, SA, Australia;(3) Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College St., London, NW1 0TU, UK |
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Abstract: | Hyaluronan (HA) is a large but simple glycosaminoglycan composed of repeating D-glucuronic acid, β1–3 linked to N-acetyl-D-glucosamine β1–4, found in body fluids and tissues, in both intra- and extracellular compartments. Despite its structural
simplicity, HA has diverse functions in skeletal biology. In development, HA-rich matrices facilitate migration and condensation
of mesenchymal cells, and HA participates in joint cavity formation and longitudinal bone growth. In adult cartilage, HA binding
to aggrecan immobilises aggrecan, retaining it at the high concentrations required for compressive resilience. HA also appears
to regulate bone remodelling by controlling osteoclast, osteoblast and osteocyte behaviour. The functions of HA depend on
its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases,
and interactions with HA-binding proteins. HA synthesis and degradation are closely regulated in skeletal tissues and aberrant
synthetic or degradative activity causes disease. The role and regulation of HA synthesis and degradation in cartilage, bone
and skeletal development is discussed.
Received 5 August 2007; received after revision 19 September 2007; accepted 20 September 2007 |
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Keywords: | Hyaluronan hyaluronan synthase hyaluronidase cartilage bone growth plate skeletal development limb morphogenesis |
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