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Unformatted text preview: 1 Lecture 10 Notes October 8, 2008 HA and aggrecan: Schwartz and Domowicz (2002) Chondrodysplasias due to proteoglycan defects. Glycobiology 12: 57R-68R Perlecan and basal laminae Notes for slides 7 and 8 Knudson (2003) HA and CD44: Strategic players for cell-matrix interactions during chondrogenesis and matrix assembly. Birth Defects Research (Part C) 69: 173-196 CD44 retains the cartilage proteoglycan aggregate in the pericellular matrix by binding to the core filament of HA. The addition of HA oligosaccharides displaces receptor-bound HA and proteoglycan aggregates. HA synthase retains a small pool of pericellular matrix components. Hexasaccharide are the smallest HA oligosaccharides that can compete for binding with endogenous cell surface HA. Incubation of cells with HA hexasaccharides (HA 6 ) displaces prebound HA from the cell surface. Incubation of HA 6 displaces 80% of the HA from the chondrocyte pericellular matrix as well as aggrecan (which is bound to HA via the G1 domain and link proteins). The remaining 20% is anchored to the HA synthase in the plasma membrane. Repeat of notes presented in lecture 9 Chondrodysplasias due to PG (aggrecan) defects Schwartz and Domowics (2002) Glycobiology 12: 57R-68R Nanomelia: a lethal chondrodystrophy of chickens Chick embryos homozygous for the autosomal recessive gene nanomelia (nm) exhibit an extreme form of micromelia with reduced trunk and head sizes and gross skeletal abnormalities including extremely shortened, broad and malformed limbs that are often twisted away from the body in a cephalad direction. Phenotypic distinctions can be observed as early as E8 and then become exaggerated with time of development., for example, trunk length (base of the skull to tail) of the mutants decreases from approximately 68% that of normal (wt) embryos at E14 to approximately 50% of normal at E20. The reduction of functional ECM is due to failure of nanomelic chondrocytes to produce aggrecan, the cartilage specific CSPG. Though nanomelic chondrocytes produce normal amounts of type II collagen and can synthesize chondroitin sulfate chains, a truncated version of the core protein is synthesized essentially missing only...
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This note was uploaded on 09/29/2009 for the course CSB csb327 taught by Professor Ringuitte during the Fall '08 term at University of Toronto- Toronto.
- Fall '08