Chondrogenesis, joint formation, and articular cartilage regeneration
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Abstract The repair of joint surface defects remains a clinical challenge, as articular cartilage has a limited healing response. Despite this, articular cartilage does have the capacity to grow and remodel extensively during pre‐ and post‐natal development. As such, the elucidation of developmental mechanisms, particularly those in post‐natal animals, may shed valuable light on processes that could be harnessed to develop novel approaches for articular cartilage tissue engineering and/or regeneration to treat injuries or degeneration in adult joints. Much has been learned through mouse genetics regarding the embryonic development of joints. This knowledge, as well as the less extensive available information regarding post‐natal joint development is reviewed here and discussed in relation to their possible relevance to future directions in cartilage tissue repair and regeneration. J. Cell. Biochem. 107: 383–392, 2009. © 2009 Wiley‐Liss, Inc.Keywords:
Chondrogenesis
Objectives: To explore the effects of cyclosporine (CsA) on skeletal development (chondrogenesis).
Materials and Methods: Mesenchymal cells obtained from stage-23 to stage-24 chick-embryo limb buds were grown in 96-well plates using chemically defined tissue-culture medium. Cultures were treated with CsA (0.01-5.0 µg/ml) and incubated (37ºC, 5% CO2) with daily medium changes for 4 days. After incubation of the cells in multiwell plate, cartilage differentiation (chondrogenesis) was assessed by selectively staining sulfated glycosaminoglycans (GAGs) in the cartilage matrix with Alcian blue, extracting the GAGs with 4 M guanidinium HCl, and spectrophotometric analysis of the extracts. Results: CsA treatment had concentration-dependent effects on chick limb-bud mesenchymal cell cultures. At 5 µg/ml, CsA caused cell loss, as judged microscopically by the paucity of cells remaining at the end of the culture period. CsA concentrations between 0.1 and 1 µg/ml caused a marked, dose-dependent decrease in chondrogenesis. At 0.01 µg/ml, CsA had no significant effect on chondrogenesis. At concentrations above 0.01 µg/ml, normalized data showed significant chondrogenic inhibition at 0.5 and 1.0 µg/ml CsA. Conclusions: The findings suggest a possible biological basis for CsA-associated effects on mesenchyme-derived tissues and provide a model system for further studies.
Materials and Methods: Mesenchymal cells obtained from stage-23 to stage-24 chick-embryo limb buds were grown in 96-well plates using chemically defined tissue-culture medium. Cultures were treated with CsA (0.01-5.0 µg/ml) and incubated (37ºC, 5% CO2) with daily medium changes for 4 days. After incubation of the cells in multiwell plate, cartilage differentiation (chondrogenesis) was assessed by selectively staining sulfated glycosaminoglycans (GAGs) in the cartilage matrix with Alcian blue, extracting the GAGs with 4 M guanidinium HCl, and spectrophotometric analysis of the extracts. Results: CsA treatment had concentration-dependent effects on chick limb-bud mesenchymal cell cultures. At 5 µg/ml, CsA caused cell loss, as judged microscopically by the paucity of cells remaining at the end of the culture period. CsA concentrations between 0.1 and 1 µg/ml caused a marked, dose-dependent decrease in chondrogenesis. At 0.01 µg/ml, CsA had no significant effect on chondrogenesis. At concentrations above 0.01 µg/ml, normalized data showed significant chondrogenic inhibition at 0.5 and 1.0 µg/ml CsA. Conclusions: The findings suggest a possible biological basis for CsA-associated effects on mesenchyme-derived tissues and provide a model system for further studies.
Chondrogenesis
Mesenchyme
Limb bud
Matrix (chemical analysis)
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Background . The ATDC5 cell line is regarded as an excellent cell model for chondrogenesis. In most studies with ATDC5 cells, insulin medium (IM) was used to induce chondrogenesis while chondrogenic medium (CM), which was usually applied in chondrogenesis of mesenchymal stem cells (MSCs), was rarely used for ATDC5 cells. This study was mainly designed to investigate the effect of IM, CM, and growth medium (GM) on chondrogenesis of ATDC5 cells. Methods . ATDC5 cells were, respectively, cultured in IM, CM, and GM for a certain time. Then the proliferation and the chondrogenesis progress of cells in these groups were analyzed. Results . Compared with CM and GM, IM promoted the proliferation of cells significantly. CM was effective for enhancement of cartilage specific markers, while IM induced the cells to express endochondral ossification related genes. Although GAG deposition per cell in CM group was significantly higher than that in IM and GM groups, the total GAG contents in IM group were the most. Conclusion . This study demonstrated that CM focused on induction of chondrogenic differentiation while IM was in favor of promoting proliferation and expression of endochondral ossification related genes. Combinational use of these two media would be more beneficial to bone/cartilage repair.
Chondrogenesis
Endochondral ossification
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Articular cartilage (AC) is the main focus of this chapter and indeed most cartilage regeneration studies, since it is commonly affected by diseases and traumatic injuries that necessitate its therapeutic regeneration. There are four main approaches for cartilage regeneration: cultured cell implantation, engineered tissue construct implantation, scaffoldless tissue regeneration, and guided tissue regeneration. Cartilage growth, development, and repair are dependent on both biomechanical and biological signals. The most important growth factors used in cartilage regeneration and tissue engineering approaches are the transforming growth factor ß (TGF-ß) family members, particularly TGF-ß1 and TGF-ß3. Overall, new strategies in the field of cartilage regeneration focus on the unique biochemical and physical properties of native cartilage to design novel tissue constructs that are decorated with cartilage-specific signals and display suitable anatomical geometries and mechanical properties for the treatment of large tissue defects.
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NF-κB/p65 has been reported to be involved in regulation of chondrogenic differentiation. However, its function in relation to key chondrogenic factor Sox9 and onset of chondrogenesis during endochondral ossification is poorly understood. We hypothesized that the early onset of chondrogenic differentiation is initiated by transient NF-κB/p65 signaling.
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Chondrogenesis
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Introduction: Chondrogenic differentiation of canine MSCs (cMSCs) has been described using the classic micromass technique. However, cMSCs appear to respond inconsistently using this method. The objectives of this study were (1) to develop a collagen-based 3D serum-free system to facilitate consistent cMSC chondrogenic cultures; (2) to qualitatively and quantitatively assess the effect of various chondrogenic media on cMSC chondrogenesis.
Chondrogenesis
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Abstract. Demineralized bone matrix contains factors which stimulate chondrogenesis and osteogenesis in vivo. A water‐soluble extract of bone has been shown to stimulate chondrogenesis in vitro in embryonic limb mesenchymal cells (Syftestad, Lucas & Caplan, 1985). The aim of this study was to analyse the cellular mechanism of the bone‐derived chondrogenesis‐stimulating activity, with particular attention on how normal requirements for chondrogenesis may be altered. The effects of bovine bone extract (BBE) on chondrogenesis in vitro were studied using micromass cultures of chick limb bud mesenchyme isolated from embryos at Hamburger‐Hamilton (HH) stage 23/24, an experimental system which is capable of undergoing chondrogenic differentiation. Bovine diaphyseal long bones were demineralized and extracted with guanidine‐HCl to prepare BBE (Syftestad & Caplan, 1984). High‐density mesenchyme cultures (30 times 10 6 cells/ml) were exposed to different doses of BBE (0–01‐1‐0 mg ml ‐1 ) and chondrogenesis was quantified based on cartilage nodule number and [ 35 S]sulphate incorporation. BBE was tested on micromass cultures of varying plating densities (2–30 times 10 6 cells/ml), on cultures of ‘young’ limb bud cells (HH stage 17/18), and on cultures enriched with chondroprogenitor cells obtained from subridge mesoderm. Since poly‐L‐lysine (PL) has recently been shown (San Antonio & Tuan, 1986) to promote chondrogensis, PL and BBE were introduced together in different doses, in the culture medium, to determine if their actions were synergistic. Our results show that BBE stimulates chondrogenesis in a dose‐dependent manner and by a specific, direct action on the chondroprogenitor cells but not in normally non‐chondrogenic, low density or ‘young’ limb bud cell cultures. The effects of PL and BBE are additive and these agents appear to act by separate mechanisms to stimulate chondrogenesis; PL primarily enhances nodule formation, and BBE appears to promote nodule growth.
Chondrogenesis
Mesenchyme
Limb bud
Matrix (chemical analysis)
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Regenerative Medicine
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Chondrogenesis
Limb bud
Tretinoin
Mesenchyme
Matrix (chemical analysis)
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Chondrogenesis
SOX9
RUNX2
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