Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer

Wang, Qiwei; Chen, Zhaolie; Piao, Yongjun

doi:10.1263/jbb.100.418

Cited by 132 publications

(104 citation statements)

References 12 publications

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“…37 Of note, TIMP-1 and À2 were shown to increase expression at the edges of acutely ruptured tendons further supporting the difference in tendon response to acute versus chronic injury. 33,38 The variability of these past results further confirm the theory that an important interplay exists between the matrix reassembly activity of MMPs and the inhibitory effects of TIMPs on that process. We report that GDF-5 induced a decrease in MMP-3 expression at day 3 followed by a large increase at day 6, as well as moderate variable changes in MMP-13 and TIMP-2 at varying times and concentrations.…”

Section: Fig 11supporting

confidence: 59%

“…This temporal relationship is consistent with the roles of collagen in tendon formation-Col I is the primary collagen secreted by mature tenocytes, while Col III plays a role in early wound healing and in endotenon and epitenon formation. 38 Additionally, OHP was increased in ADMSCs treated with GDF-5 versus control at day 12, providing biochemical evidence that GDF-5 induced increased collagen production. Because a tendon's extracellular environment is critical to its function, we then investigated the effect of GDF-5 on various ECM components produced by ADMSCs.…”

Section: Fig 11mentioning

confidence: 87%

“…Because the highly differentiated and minimally proliferative nature of tenocytes presents a significant limitation with regard to neotendon formation at injury sites, 38 ADMSCs treated with GDF-5 may prove to be a superior cell source in this regard.…”

Section: Fig 11mentioning

confidence: 99%

See 2 more Smart Citations

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

Park

Hogan

Kesturu

et al. 2010

Tissue Engineering Part A

142

132

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Section: Fig 11supporting

confidence: 59%

Section: Fig 11mentioning

confidence: 87%

See 1 more Smart Citation

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

Park

Hogan

Kesturu

et al. 2010

Tissue Engineering Part A

142

132

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“…As members of the TGF-b superfamily, these proteins induce tenocyte differentiation of bone marrow mesenchymal cells [48]. Receptor binding triggers members of the Smad family of nuclear transcription factors, including Smad-1, -5, and -8.…”

Section: Discussionmentioning

confidence: 99%

The Effects of GDF-5 and Uniaxial Strain on Mesenchymal Stem Cells in 3-D Culture

Farng

Urdaneta²,

Barba³

et al. 2008

Clin Orthop Relat Res

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Recent endeavors in tissue engineering have attempted to identify the optimal parameters to create an artificial ligament. Both mechanical and biochemical stimulation have been used by others to independently modulate growth and differentiation, although few studies have explored their interactions. We applied previously described fabrication techniques to create a highly porous (90%-95% porosity, 212-300 lm), 3-D, bioabsorbable polymer scaffold (polycaprolactone). Scaffolds were coated with bovine collagen, and growth and differentiation factor 5 (GDF-5) was added to half of the scaffolds. Scaffolds were seeded with mesenchymal stem cells and cultured in a custom bioreactor under static or cyclic strain (10% strain, 0.33 Hz) conditions. After 48 hours, both mechanical stimulation and GDF-5 increased mRNA production of collagen I, II, and scleraxis compared to control; tenascin C production was not increased. Combining stimuli did not change gene expression; however, cellular metabolism was 1.7 times higher in scaffolds treated with both stimuli. We successfully grew a line of mesenchymal stem cells in 3-D culture, and our initial data indicate mechanical stimulation and GDF-5 influenced cellular activity and mRNA production; we did not, however, observe additive synergism with the mechanical and biological stimuli.

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“…Depletion of Bgn and Fmod in mice leads to decreased expression of the tendon marker scleraxis (Scx) and of Type I collagen, and increased sensitivity to BMP2 in TSPCs when compared to cells from wild-type mice [18]. BMP12 acts as signaling molecules during embryonic tendon/ligament formation in animal experiments [67,112,114] and can stimulate patellar tendon fibroblasts proliferation in humans [40]. Expression of Scx, a member of the basic helix-loop-helix (bHLH) superfamily of transcription factors in the progenitors and cells of all tendon tissues [94], is crucial for differentiation of all force-transmitting and intermuscular tendons in Scx -/-mice [78] and for activation of the COL1a1 gene in mouse tendon fibroblasts in an in vitro study [63].…”

Section: Tendon Cellsmentioning

confidence: 99%

The Basic Science of Tendinopathy

Murrell

2008

Clinical Orthopaedics &Amp; Related Research

314

254

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Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the ''dose'' of load to the tendon enthesis -including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.

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Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer

Cited by 132 publications

References 12 publications

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

The Effects of GDF-5 and Uniaxial Strain on Mesenchymal Stem Cells in 3-D Culture

The Basic Science of Tendinopathy

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