Wednesday, November 25, 2009

Misc Stem Cell types to chondrocytes

Chondrogenic Differentiation of Amniotic Fluid Stem Cells and Their Potential for Regenerative Therapy.

"Chondrocytes constituting articular cartilage show some functional and structural differences from growth plate chondrocytes. Whereas the latter undergo highly dynamic changes as long bone growth persists, articular cartilage chondocytes provide continuous function throughout life. Articular chondrocytes originate from a pool of growth differentiation factor 5 (GDF5) positive progenitor cells and that growth plate chondrocytes are derived from GDF5 negative cell populations"

"GDF5 expression is first evident in the mesenchymal interzone of early joints. The interzone is an essential regulator region and it has been widely assumed that it is responsible for formation of joint structures including articular cartilage, ligaments and synovial lining. Interzone cells express a number of genes able to control joint development, like: GDF5, WNT5A, WNT4, GLI3{up in LSJL}, CD44, ERG{up} and NOGGIN. GDF5 has chondrogenic activity, whereas WNT ligands and NOGGIN are anti-chondrogenic"

"Joint cavitation involves differential hyaluronan synthesis under the influence of mechanical stimuli. The hyaluronan receptor, CD44, is expressed at the joint interzone and at developing articular surfaces and it induces cell adhesion as well as cell separation, depending on the concentration of hyaluronan"

"Mature articular cartilage consists of three zones: the superficial zone, where small and flat chondrocytes reside and collagen fibrils are orientated parallel to the surface, the transitional zone, representing the thickest part of cartilage, where collagen fibers are less organized, and the radial zone, where fibers are orientated perpendicular to the surface and oxygen tension is below 1 %. Underneath is the tidemark, which delineates hyaline articular cartilage from calcified cartilage."

" Upon hypertrophy, growth plate chondrocytes downregulate SOX9 and type II collagen expression, whereas RUNX2, type X collagen, alkaline phosphatase and VEGFA are upregulated"

"[Amniotic Fluid Stem Cells] can be expanded in cell culture and show expression of CD29, CD44, CD73, CD90, CD105 and SSEA4 with over 90 % of cells being positive for OCT4"

"supplementation of chondrogenesis promoting factors is necessary for successful manipulation of AFS cells and that the isolation of c-kit positive cells also enhances the differentiation process."

"GDF5 over-expression results in cartilage overgrowth and joint fusion in vivo"

"WNT-4, WNT-14, WNT-16 and the WNT signaling mediator β-catenin also show anti-chondrogenic activity during joint formation"

"up regulation of HIF1α (hypoxia-inducible factor) and HIF2α is essential for SOX9 expression"

"In articular cartilage autophagy plays an important role, since it protects chondrocytes from age related cell death and preserves homeostasis within the tissue{perhaps in growth plate chondrochytes as well}. During aging-related intracellular changes, biochemical stimuli as well as mechanical stress can lead to OA and during this process the competence to undergo autophagy is lost"<-mTor is involved in the regulation of growth plate autophagy.  Proteoglycan sulfation can determine the efficience of chondrocyte autophagy.

"The induction of autophagy is able to prevent ageing related degenerations."<-maybe autophagy can prevent epiphyseal fusion since epiphyseal fusion is an aging related degeneration.

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