Bone cell–matrix protein interactions

Marie, Pierre J.

doi:10.1007/s00198-009-0856-7

Cited by 19 publications

(10 citation statements)

References 68 publications

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“…These bioactive molecules are responsible for signaling processes that actively modulate cell behavior through cell/matrix interactions to maintain tissue homeostasis (Discher, Mooney, & Zandstra, ; Guilak et al, ; Reilly & Engler, ). For instance, in the context of skeletal tissue, bone ECM is produced secreted by osteoblasts differentiated from mesenchymal stromal cells (MSCs), which secrete and mineralize the surrounding ECM, giving structural support to the skeletal tissue and regulating cellular processes to maintain bone integrity (Alford & Hankenson, ; Marie, ; Sommerfeldt & Rubin, ). Thus the peculiar composition of bioactive molecules makes the ECM far from being an inert cellular support (Hynes, ).…”

Section: Introductionmentioning

confidence: 99%

Comparative proteomic profiling of human osteoblast‐derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization

Baroncelli

Eerden

Kan

et al. 2017

Journal Cellular Physiology

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The extracellular matrix (ECM) is a dynamic component of tissue architecture that physically supports cells and actively influences their behavior. In the context of bone regeneration, cellsecreted ECMs have become of interest as they reproduce tissue-architecture and modulate the promising properties of mesenchymal stem cells (MSCs). We have previously created an in vitro model of human osteoblast-derived devitalized ECM that was osteopromotive for MSCs. The aim of this study was to identify ECM regulatory proteins able to modulate MSC differentiation to broaden the spectrum of MSC clinical applications. To this end, we created two additional models of devitalized ECMs with different mineralization phenotypes. Our results showed that the ECM derived from osteoblast-differentiated MSCs had increased osteogenic potential compared to ECM derived from undifferentiated MSCs and non-ECM cultures. Proteomic analysis revealed that structural ECM proteins and ribosomal proteins were upregulated in the ECM from undifferentiated MSCs. A similar response profile was obtained by treating osteoblast-differentiating MSCs with Activin-A. Extracellular proteins were upregulated in Activin-A ECM, whereas mitochondrial and membrane proteins were downregulated. In summary, this study illustrates that the composition of different MSC-secreted ECMs is important to regulate the osteogenic differentiation of MSCs. These models of devitalized ECMs could be used to modulate MSC properties to regulate bone quality. K E Y W O R D SActivin-A, bone regeneration, extracellular matrix, mesenchymal stromal cells Due to the role of the ECM on actively modulating MSC osteogenic differentiation and to the increasing interest of using MSCs for cell-based therapies, the aim of our study was to identify ECM proteins that are involved in osteoblast differentiation and mineralization making these proteins suitable candidates to control bone quality. To this end, we created in vitro ECM models with extremely different mineralization phenotypes, in order to get more insights into the effect of the ECM composition on MSC behavior.We have previously created an in vitro model of human MSC- 2 | MATERIALS AND METHODS | Cell culture and ECM preparationsHuman bone marrow-derived MSCs were used to produce the devitalized ECM as previously described (Baroncelli M., unpublished data). Briefly, commercially available MSCs (PT-2501, Lonza, Walkersville, MD) from a single donor at passage 7, were cultured in growth media (alpha-Mem phenol-red free (GIBCO, Paisley, UK), 10% fetal bovine serum) for 2 days. Then, MSCs were cultured for 11 days by supplementing the growth medium with 100 nM dexamethasone and 10 mM β-glycerophosphate (Sigma, St. Louis, MO) to induce the osteogenic differentiation. MSCs were devitalized before the onset of mineralization by freeze-thaw cycles and DNAse treatment (10 U/ml; Sigma-Aldrich), followed by extensive washings with Phosphate Buffer Saline (PBS, Gibco BRL, Carlsbad, CA) and sterile air drying, before freezing and subsequent use.In ...

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Section: Introductionmentioning

confidence: 99%

Comparative proteomic profiling of human osteoblast‐derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization

Baroncelli

Eerden

Kan

et al. 2017

Journal Cellular Physiology

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“…In bone tissue, the extracellular matrix (ECM) is composed of proteins that promote cell adhesion, and growth factors such as BMPs that promote cell differentiation (Chen et al, 2004; Wagner et al, 2010). These various proteins exhibit different distributions (Marie, 2009). In addition to the extracellular antagonists controlling the binding of the ligand to receptor complexes to regulate BMP signaling (Sengle et al, 2008), different adhesion components of ECM modulate BMP signaling (Wang et al, 2008; Hynes, 2009).…”

Section: Introductionmentioning

confidence: 99%

Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling

et al. 2013

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SummaryMature osteoblasts are the cells responsible for bone formation and are derived from precursor osteoblasts. However, the mechanisms that control this differentiation are poorly understood. In fact, unlike the majority of organs in the body, which are composed of “soft” tissue from which cells can easily be isolated and studied, the “hard” mineralized tissue of bone has made it difficult to study the function of bone cells. Here, we established an in vitro model that mimics this differentiation under physiological conditions. We obtained mature osteoblasts and characterized them on the basis of the following parameters: the strong expression of osteoblastic markers, such as Runx2 and Col-I; the achievement of specific dimensions (the cell volume increases 26-fold compared to the osteoblast precursors); and the production of an abundant extracellular matrix also called osteoid. We demonstrated that the differentiation of osteoblast precursors into mature osteoblasts requires the continuous activation of Bone Morphogenetic Protein (BMP) receptors, which we established with the immobilization of a BMP-2mimetic peptide on a synthetic matrix mimicking in vivo microenvironment. Importantly, we demonstrated that the organization of the F-actin network and acetylated microtubules of the cells were modified during the differentiation process. We showed that the perturbation of the F-actin cytoskeleton organization abolished the differentiation process. In addition, we demonstrated that expression of the Runx2 gene is required for this differentiation. These findings demonstrate the retro-regulation of cytoplasmic and genic components due to the continuous induction of BMP-2 and also provide more detailed insights into the correct signaling of BMPs for cell differentiation in bone tissue.

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“…3 Cell proliferation, differentiation and apoptosis in osteoblasts are regulated by a variety of signalling pathways induced by diffusible factors and cell-matrix interactions. 4,5 In addition, there is growing evidence that cell-cell contacts mediated by cadherins can modulate osteoblastogenesis and bone formation. 6,7 The mechanisms underlying the regulatory effect of cadherins in cells of the osteoblast lineage are now better understood.…”

Section: Introductionmentioning

confidence: 99%

Cadherins and Wnt signalling: a functional link controlling bone formation

Marie¹,

Haÿ²

2013

BoneKEy Reports

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Cadherins are calcium-dependent cell adhesion molecules that have a major role in morphogenesis and tissue formation. In bone, cadherins control osteoblast differentiation by mediating cell-cell adhesion and signals that promote phenotypic osteoblast gene expression. Furthermore, cadherins can interact with Wnt signalling to modulate osteoblastogenesis. One mechanism involves the interaction of N-cadherin with β-catenin at the cell membrane, resulting in β-catenin sequestration, reduction of the cytosolic β-catenin pool and inhibition of Wnt signalling. In addition to modulating the β-catenin pool, N-cadherin can regulate osteoblasts by interacting with the Wnt coreceptors LRP5 or LRP6. We showed that the functional interaction between N-cadherin and LRP5/6 in osteoblasts promotes β-catenin degradation and reduces canonical Wnt signalling. This crosstalk between N-cadherin and Wnt signalling has a negative impact on osteoblast proliferation, differentiation and survival, independently of cell-cell adhesion, which results in decreased bone formation and delayed bone accrual in mice. The identification of this crosstalk between N-cadherin and Wnt signalling may have therapeutic implications, as a disruption of the N-cadherin-LRP5/6 interaction using a competitor peptide can increase Wnt/β-catenin signalling without affecting cell-cell adhesion, and this effect results in increased osteoblastogenesis and bone tissue formation in vivo. In this review, we summarize our current knowledge of the key crosstalks between cadherins and Wnt signalling that impact osteoblast function, bone formation and bone mass, and the possible therapeutic implications of such interactions for promoting osteoblastogenesis, bone formation and bone mass.

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Bone cell–matrix protein interactions

Cited by 19 publications

References 68 publications

Comparative proteomic profiling of human osteoblast‐derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization

Comparative proteomic profiling of human osteoblast‐derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization

Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling

Cadherins and Wnt signalling: a functional link controlling bone formation

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