Why cellular stress suppresses adipogenesis in skeletal tissue, but is ineffective in adipose tissue: Control of mesenchymal cell differentiation via integrin binding sites in extracellular matrices

Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA. Electronic address: .
Matrix biology: journal of the International Society for Matrix Biology (Impact Factor: 5.07). 06/2013; 32(7). DOI: 10.1016/j.matbio.2013.06.001
Source: PubMed


This Perspective addresses one of the major puzzles of adipogenesis in adipose tissue, namely its resistance to cellular stress. It introduces a concept of "density" of integrin binding sites in extracellular matrix, proposes a cellular signaling explanation for the observed effects of matrix elasticity and of cell shape on mesenchymal stem cell differentiation, and discusses how specialized integrin binding sites in collagen IV - containing matrices guard two pivotal physiological and evolutionary processes: stress-resistant adipogenesis in adipose tissues and preservation of pluripotency of mesenchymal stem-like cells in their storage niches. Finally, it proposes strategies to suppress adipogenesis in adipose tissues.

Download full-text


Available from: Bjorn R Olsen, Jan 04, 2014
15 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Despite detailed knowledge about the structure and signaling properties of individual collagen receptors, much remains to be learned about how these receptors participate in linking cells to fibrillar collagen matrices in tissues. In addition to collagen-binding integrins, a group of proteins with affinity both for fibrillar collagens and integrins link these two protein families together. We have introduced the name COLINBRI (COLlagen INtegrin BRIdging) for this set of molecules. Whereas collagens are the major building blocks in tissues and defects in these structural proteins have severe consequences for tissue integrity, the mild phenotypes of the integrin type of collagen receptors have raised questions about their importance in tissue biology and pathology. Scope of review: We will discuss the two types of cell linkages to fibrillar collagen (direct- versus indirect COLINBRI-mediated) and discuss how the parallel existence of direct and indirect linkages to collagens may ensure tissue integrity. Major conclusions: The observed mild phenotypes of mice deficient in collagen-binding integrins and the relatively restricted availability of integrin-binding sequences in mature fibrillar collagen matrices support the existence of indirect collagen-binding mechanisms in parallel with direct collagen binding in vivo. General significance: A continued focus on understanding the molecular details of cell adhesion mechanisms to collagens will be important and will benefit our understanding of diseases like tissue- and tumor fibrosis where collagen dynamics are disturbed. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
    Biochimica et Biophysica Acta 12/2013; 1840(8). DOI:10.1016/j.bbagen.2013.12.022 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dental follicle cells (DFCs) are ideal for studies concerning the differentiation of dental precursor cells into alveolar osteoblasts and cementoblasts. Previous investigations have suggested that the extracellular matrix (ECM) protein laminin and the ECM receptor integrin-α2/-β1 play regulatory roles during the osteogenic differentiation of DFCs. Our present data indicate that laminin impairs alkaline phosphatase (ALP) activity following osteogenic induction while inducing integrin-α2/-β1 expression, osteogenic differentiation marker elevation, and DFC biomineralization. Integrin-α2/-β1 facilitates the laminin-dependent expression of osteogenic differentiation markers and the laminin-dependent inhibition of ALP activity. Moreover, these laminin-dependent effects on the osteogenic differentiation of DFCs can be reversed by the inhibition of the FAK/ERK signaling pathway. Thus, laminin regulates the inhibition of early osteogenic differentiation markers and the induction of late osteogenic differentiation markers via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway.
    Cell and Tissue Research 05/2014; 357(1). DOI:10.1007/s00441-014-1869-x · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Systemic sclerosis (scleroderma) is a chronic inflammatory disease that leads to fibrosis of the skin and involved internal organs. No efficient therapy is currently available. This review summarizes recent progress made in basic as well as clinical science and concludes with a concept that therapy targeting fibrosis in scleroderma needs to take into account the global microenvironment in the skin with its diverse cellular players interacting with a complex extracellular matrix environment and matrix-associated growth factors.
    Journal of Molecular Medicine 07/2014; 92(9). DOI:10.1007/s00109-014-1190-x · 5.11 Impact Factor