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Integrin-mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix.
S Gronthos1, P J Simmons, S E Graves
1Craniofacial & Skeletal Diseases Branch, National Institute of Dental & Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. sgronthos@dir.nidcr.nih.gov
Bone
|February 22, 2001
Summary
Bone marrow stromal cells use beta1 integrins to interact with the extracellular matrix, influencing their growth and development into bone-forming cells. This study highlights beta1 integrins as key regulators of stromal precursor cell function.
Area of Science:
- Cell Biology
- Biochemistry
- Hematology
Background:
- Bone marrow stromal cells (BMSCs) are crucial for hematopoiesis and osteogenesis.
- Interactions between BMSCs and the extracellular matrix (ECM) via integrins are vital for cell development but not fully understood.
Purpose of the Study:
- To investigate the role of integrins in mediating bone marrow stromal precursor cell adhesion and proliferation.
- To determine the specific integrin subtypes involved in BMSC interactions with ECM components.
- To explore the function of integrins in BMSC differentiation into osteoblasts.
Main Methods:
- Purification of STRO-1-positive human bone marrow stromal precursor cells using fluorescence-activated cell sorting.
- Assessing clonogenic growth in response to various ECM ligands (fibronectin, vitronectin, laminin, collagen).
- Flow cytometry analysis for integrin expression (e.g., alpha1beta1, alpha2beta1, alpha5beta1, alpha6beta1, alpha(v)beta3, alpha(v)beta5, alpha4beta1).
- Functional blocking antibody assays to inhibit specific integrin heterodimers.
- Culture of BMSCs under osteoinductive conditions with integrin blocking antibodies.
Main Results:
- BMSC progenitors showed differential adhesion to fibronectin, vitronectin, and laminin, with higher affinity for collagen type IV than types I and III.
- Multiple beta1 integrins (alpha1beta1, alpha2beta1, alpha5beta1, alpha6beta1) and alpha(v) integrins (alpha(v)beta3, alpha(v)beta5) were expressed on stromal precursors.
- Stromal cell proliferation on collagen, laminin, and fibronectin was mediated by beta1 integrins; vitronectin adhesion involved alpha(v)beta3.
- Blocking beta1 integrins significantly reduced osteogenic matrix formation in vitro.
Conclusions:
- Beta1 integrins are the primary adhesion receptors for bone marrow stromal precursor cells interacting with ECM glycoproteins.
- These integrins play a significant role in BMSC proliferation and adhesion within the bone marrow microenvironment.
- The beta1 integrin subfamily is implicated in the differentiation of stromal precursor cells into osteoblast-like cells.