Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition

Buxton, Paul; Bitar, Malak; Gellynck, Kris; Parkar, MH; Brown, RA; Young, Alison; Knowles, Jonathan C.; Nazhat, Showan N.

doi:10.1016/j.bone.2008.03.028

Cited by 72 publications

(72 citation statements)

References 38 publications

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“…The balance between bone formation and resorption is partly regulated by MMPs. In this setting, gene expression of osteogenic markers such as ALP and BSP can be substantially decreased in dense collagen gels treated with a broad spectrum MMP inhibitor [Buxton et al, 2008]. In turn, overexpression of Runx-2, a transcription factor involved in osteoblast , Bone mineralization; OB, osteoblast; col, collagen.…”

Section: Discussionmentioning

confidence: 97%

“…It also initiates a signaling cascade leading to dephosphorylation of Akt and subsequently to cell apoptosis [Fujisaki and Hattori, 2002]. Indeed, primary osteoblastic cells cultured in 3D collagen lattices exhibit a low rate of proliferation, and cell death occurs at the end of contraction phase [Buxton et al, 2008]. The balance between bone formation and resorption is partly regulated by MMPs.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the ability of osteoblasts to contract type I collagen matrices may help to bridge fractured bone cortices. A series of investigations using clonal cell lines, rat or human osteosarcoma cell lines, bone marrow cells from rat femur or isolated from the calvaria of neonatal mice, highlighted the contribution of mechanical forces in 3D collagen lattices in promoting the appearance of an osteoblastic phenotype and in accelerating the mineralization of the matrix [Akhouayri et al, 1999;Buxton et al, 2008;Parreno et al, 2008]. During contraction of collagen lattices, a 2 b 1 integrin acts as a mechano-receptor and initiates signaling cascades that leads to the up-regulation of MMP-1 as observed in fibroblasts and several osteosarcoma cell lines [Langholz et al, 1995;Riikonen et al, 1995].…”

Section: Discussionmentioning

confidence: 99%

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Mechanical forces‐induced human osteoblasts differentiation involves MMP‐2/MMP‐13/MT1‐MMP proteolytic cascade

Barthelemi

Robinet

Garnotel

et al. 2012

J of Cellular Biochemistry

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Matrix metalloproteinase (MMP) family proteins play diverse roles in many aspects of cellular processes such as osteoblastic differentiation. Besides, mechanical forces that occur in 3D collagen gel promote the osteoblastic phenotype and accelerate matrix mineralization. Although MMPs have been involved in bone differentiation, the proteolytic cascades triggered by mechanical forces are still not well characterized. In this study, we have investigated the contribution of both proteolytic cascades, MMP-3/MMP-1 and MMP-2/MMP-13/MT1-MMP in the differentiation of human osteoblasts cultured in a floating type I collagen lattice (FL) versus an attached collagen lattice (AL). Compared to AL, contraction of human osteoblasts-populated FL led to a fast (1 day) induction of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteoprotegerin (OPG), and Runx-2 expression. At day 4, osteocalcin (OC) overexpression preceded the formation of calcium-containing nodule formation as assessed by X-ray analyses. MMP-1 and MMP-3 were produced to similar extent by cells cultured in FL and AL, whereas contraction of collagen lattices triggered both mRNA overexpression of MMP-2, MMP-13, and MT1-MMP (i.e., MMP-14), and their activation as evidenced by Western blotting or zymographic analyses. Down-regulating MT1-MMP expression or activity either by siRNA transfection or supplementation of culture medium with TIMP-1 or TIMP-2 highlighted the contribution of that enzyme in OC, ALP, and OPG expression. MMP-2 and MMP-13 were more directly involved in BSP expression. So, these results suggest that the main proteolytic cascade, MMP-2/MMP-13/MT1-MMP, and more particularly, its initial regulator MT1-MMP is involved in osteoblast differentiation through mechanical forces.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanical forces‐induced human osteoblasts differentiation involves MMP‐2/MMP‐13/MT1‐MMP proteolytic cascade

Barthelemi

Robinet

Garnotel

et al. 2012

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…86 The stiffness of the collagen matrix has also shown that it functionally stimulates implanted cell populations. 87,88 The compressive modulus of collagen-GAG scaffolds could be controlled by varying the collagen amount as well as by altering the dehydrothermal crosslinking process. 88 Specifically, the 1% collagen-GAG scaffolds that were treated with a higher crosslinking temperature exhibited increased cell numbers and metabolic activity up to 7 days after culture.…”

mentioning

confidence: 99%

“…Another study using a dense collagen matrix showed upregulation of osteogenic signal expression in primary mouse calvarial osteoblasts. 87 Osteogenic differentiation of cells in the matrix were verified through the observation of increased expressions of ALP and BSP in the first 7 days of culture in osteogenic supplemented media, which was compared with culture on a 2D plastic surface.…”

mentioning

confidence: 99%