Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells

Tsuchiya, Hiroki; Kitoh, Hiroshi; Sugiura, Fumiaki; Ishiguro, Naoki

doi:10.1016/s0006-291x(02)03026-7

Cited by 144 publications

(112 citation statements)

References 24 publications

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“…4A). Sox9 is a member of the Sox (Sry-type HMG box) gene family, which are predominantly expressed in mesenchymal condensation and cartilage, and has been shown to activate type II collagen and aggrecan (Tsuchiya et al, 2003). We observed coll 2, agg, and COMP expression at a later time point in 3D culture, consistent with an early activating role of sox9.…”

Section: Quantitative Analyses Of Chondrocyte-related Gene Expressionsupporting

confidence: 77%

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Bosnakovski

Mizuno

Kim

et al. 2006

Biotech & Bioengineering

444

322

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Bone marrow mesenchymal stem cells (MSCs) are candidate cells for cartilage tissue engineering. This is due to their ability to undergo chondrogenic differentiation after extensive expansion in vitro and stimulation with various biomaterials in three-dimensional (3-D) systems. Collagen type II is one of the major components of the hyaline cartilage and plays a key role in maintaining chondrocyte function. This study aimed at analyzing the MSC chondrogenic response during culture in different types of extracellular matrix (ECM) with a focus on the influence of collagen type II on MSC chondrogenesis. Bovine MSCs were cultured in monolayer as well as in alginate and collagen type I and II hydrogels, in both serum free medium and medium supplemented with transforming growth factor (TGF) b1. Chondrogenic differentiation was detected after 3 days of culture in 3-D hydrogels, by examining the presence of glycosaminoglycan and newly synthesized collagen type II in the ECM. Differentiation was most prominent in cells cultured in collagen type II hydrogel, and it increased in a timedependent manner. The expression levels of the of chondrocyte specific genes: sox9, collagen type II, aggrecan, and COMP were measured by quantitative ''Real Time'' RT-PCR, and genes distribution in the hydrogel beads were localized by in situ hybridization. All genes were upregulated by the presence of collagen, particularly type II, in the ECM. Additionally, the chondrogenic influence of TGF b1 on MSCs cultured in collagenincorporated ECM was analyzed. TGF b1 and dexamethasone treatment in the presence of collagen type II provided more favorable conditions for expression of the chondrogenic phenotype. In this study, we demonstrated that collagen type II alone has the potential to induce and maintain MSC chondrogenesis, and prior interaction with TGF b1 to enhance the differentiation.

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Section: Quantitative Analyses Of Chondrocyte-related Gene Expressionsupporting

confidence: 77%

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Bosnakovski

Mizuno

Kim

et al. 2006

Biotech & Bioengineering

444

322

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“…Tsuchiya et al [103] investigated chondrogenesis of cell-mediated therapy involving sox9 gene delivery as a new treatment regimen for cartilage regeneration. Sox9 is a member of the family of Sox (Sry-type HMG box) genes and plays a key role in chondrogenesis and skeletogenesis.…”

Section: Genetic Manipulation Of Mesenchymal Stem Cells To Promote Thmentioning

confidence: 99%

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Reiser

Zhang

Hemenway

et al. 2005

Expert Opinion on Biological Therapy

166

114

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The intriguing biology of stem cells and their vast clinical potential is emerging rapidly for gene therapy. Bone marrow stem cells, including the pluripotent haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and possibly the multipotent adherent progenitor cells (MAPCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineagesn and, at least in vitro, have significant expansion capability. The apparently high self-renewal potential makes them strong candidates for delivering genes and restoring organ systems function. However, the high proliferative potential of MSCs, now presumed to be self-renewal, may be more apparent than real. Although expanded MSCs have great proliferation and differentiation potential in vitro, there are limitations with the biology of these cells in vivo. So far, expanded MSCs have failed to induce durable therapeutic effects expected from a true self-renewing stem cell population. The loss of in vivo self-renewal may be due to the extensive expansion of MSCs in existing in vitro expansion systems, suggesting that the original stem cell population and/or properties may no longer exist. Rather, the expanded population may indeed be heterogeneous and represents several generations of different types of mesenchymal cell progeny that have retained a limited proliferation potential and responsiveness for terminal differentiation and maturation along mesenchymal and non-mesenchymal lineages. Novel technology that allows MSCs to maintain their stem cell function in vivo is critical for distinguishing the elusive stem cell from its progenitor cell populations. The ultimate dream is to use MSCs in various forms of cellular therapies, as well as genetic tools that can be used to better understand the mechanisms leading to repair and regeneration of damaged or diseased tissues and organs.

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“…This list includes the replacement of genes to correct acquired or inherited disorders of bone, muscle, or cartilage by transfer of genes encoding bone morphogenic proteins -2, -4, -9 [21,[32][33][34][35][36][37][38][39][40], the transfer of genes encoding the blood coagulation factors VIII and IX for the treatment of hemophilia [41][42][43][44][45][46][47], human growth hormone [46,48], insulin-like growth factor 1 [49], and interleukin-3 [50]. This list also includes: erythropoietin [51], α-l-iduronidase for treatment of mucopolysaccharidosis type I [52], proα2 collagen (I) for treatment of osteogenesis imperfecta [53], sox9 [54] to enhance chondrogenesis, and interferon to treat tumors [55]. In several of these studies retroviral-based vectors were utilized, thereby increasing the risk of inducing insertional mutagenesis.…”

Section: ® Original Articlementioning

confidence: 99%

Transfer and Stable Transgene Expression of a Mammalian Artificial Chromosome into Bone Marrow‐Derived Human Mesenchymal Stem Cells

Vanderbyl¹,

MacDonald²,

Sidhu³

et al. 2004

STEM CELLS

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Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells

Cited by 144 publications

References 24 publications

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Transfer and Stable Transgene Expression of a Mammalian Artificial Chromosome into Bone Marrow‐Derived Human Mesenchymal Stem Cells

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