Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartila...Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.展开更多
Knee osteoarthritis is the most common joint disease.It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems.Despite ongoing research,there is a lack of know...Knee osteoarthritis is the most common joint disease.It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems.Despite ongoing research,there is a lack of knowledge regarding disease mechanisms,biomarkers,and possible cures.Current treatments do not fulfill patients’long-term needs,and it often requires invasive surgical procedures with subsequent long periods of rehabilitation.Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area.Potential cell sources to accomplish this goal include embryonic stem cells,mesenchymal stem cells,or induced pluripotent stem cells.The differentiation of stem cells into different tissue types is complex,and a suitable concentration range of specific growth factors is vital.The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development.Thus,morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage.In this review,we have summarized the problems with current treatments,potential cell sources for cell therapy,reviewed the progress of new treatments within the regenerative cartilage field,and highlighted the importance of cell quality,characterization assays,and chemically defined protocols.展开更多
文摘Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.
基金Most funding by Cline Scientific AB and partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement RESTORE no 814558 and AUTOCRAT no 874671.
文摘Knee osteoarthritis is the most common joint disease.It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems.Despite ongoing research,there is a lack of knowledge regarding disease mechanisms,biomarkers,and possible cures.Current treatments do not fulfill patients’long-term needs,and it often requires invasive surgical procedures with subsequent long periods of rehabilitation.Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area.Potential cell sources to accomplish this goal include embryonic stem cells,mesenchymal stem cells,or induced pluripotent stem cells.The differentiation of stem cells into different tissue types is complex,and a suitable concentration range of specific growth factors is vital.The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development.Thus,morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage.In this review,we have summarized the problems with current treatments,potential cell sources for cell therapy,reviewed the progress of new treatments within the regenerative cartilage field,and highlighted the importance of cell quality,characterization assays,and chemically defined protocols.
