Emerging tools to study proteoglycan function during skeletal development
- Brown, D.S., Eames, B.F.
- Methods in cell biology 134: 485-530 (Chapter)
- Registered Authors
- Brown, Daniel, Eames, Brian F.
- Bone, Cartilage, Chondroitin sulfate, Fourier-transformed infrared, Growth factor, Proteoglycans, Synchrotron imaging, Transgenics, X-ray fluorescence
- MeSH Terms
- Cartilage, Articular/metabolism*
- Cartilage, Articular/pathology
- Chondroitin Sulfate Proteoglycans/biosynthesis
- Chondroitin Sulfate Proteoglycans/genetics*
- Chondroitin Sulfate Proteoglycans/metabolism*
- Disease Models, Animal
- Extracellular Matrix/genetics
- Extracellular Matrix/metabolism
- 27312503 Full text @ Meth. Cell. Biol.
Brown, D.S., Eames, B.F. (2016) Emerging tools to study proteoglycan function during skeletal development. Methods in cell biology. 134:485-530.
In the past 20years, appreciation for the varied roles of proteoglycans (PGs), which are specific types of sugar-coated proteins, has increased dramatically. PGs in the extracellular matrix were long known to impart structural functions to many tissues, especially articular cartilage, which cushions bones and allows mobility at skeletal joints. Indeed, osteoarthritis is a debilitating disease associated with loss of PGs in articular cartilage. Today, however, PGs have a demonstrated role in cell biological processes, such as growth factor signalling, prompting new perspectives on the etiology of PG-associated diseases. Here, we review diseases associated with defects in PG synthesis and sulfation, also highlighting current understanding of the underlying genetics, biochemistry, and cell biology. Since most research has analyzed a class of PGs called heparan sulfate PGs, more attention is paid here to studies of chondroitin sulfate PGs (CSPGs), which are abundant in cartilage. Interestingly, CSPG synthesis is tightly linked to the cell biological processes of secretion and lysosomal degradation, suggesting that these systems may be linked genetically. Animal models of loss of CSPG function have revealed CSPGs to impact skeletal development. Specifically, our work from a mutagenesis screen in zebrafish led to the hypothesis that cartilage PGs normally delay the timing of endochondral ossification. Finally, we outline emerging approaches in zebrafish that may revolutionize the study of cartilage PG function, including transgenic methods and novel imaging techniques. Our recent work with X-ray fluorescent imaging, for example, enables direct correlation of PG function with PG-dependent biological processes.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes