Mechanisms of Mechano-Transduction within Osteoblasts
Abstract
Mechanical stimulation is crucial to the homeostasis of adult bone density and mass. The hypothesis of this proposal was that bone cells sense their mechanical environment through specific extracellular matrix (ECM) proteins (integrins) that are the ligands for these receptors. These studies focused on osteoblasts and the activation of specific integrin isotypes in response to adhesion and/or mechanical stimulation. The signal transductions system(s) responsible for mediating osteopontin, bone sialoprotein, and fibronectin gene expression in response to mechanical stimulation were examined as well as cellular response to variants in frequency, intensity, or duration of the mechanical stimuli. Both mechanical stimulation and cell adhesion specifically stimulated the expression of integrin binding proteins, yet while there are common features in the signal transduction processes, each gene was separately induced by unique mechanisms. Our data illustrate that the induction of intracellular kinase activities are related more to the specific nature of the ligand's interactions with its receptor and less with the process of cellular adhesion alone. They further demonstrate that osteoblast adhesion to different integrin ligands selectively mediates osteopontin gene expression. These data were the foundation for two new in vivo models to further define the role of mechanical stimulation on bone growth and healing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA416070
Entities
People
- Louis C. Gerstenfeld
Organizations
- Boston University Medical Campus