Stimulation of osteogenesis via mechanoinduction<br /> of the osteoblastic transcription factor Cbfa1
Journal Title: Αρχεία Ελληνικής Ιατρικής - Year 2002, Vol 19, Issue 5
Abstract
OBJECTIVE A primary goal of bone research is to understand the mechanism(s) by which mechanical forces dictate the cellular and metabolic activities of osteoblasts, the bone-forming cells. Several studies indicate that osteoblastic cells respond to physical loading by transducing signals that alter gene expression patterns. Accumulated data have documented the fundamental role of the osteoblast-specific transcription factor Cbfa1 in osteoblast differentiation and function. METHOD Primary cultures of human osteoblast-like cells were subjected to lowlevel continuous mechanical strain employing an established system for applying calibrated stretch. A combination of Northern/Western blotting, mobility-shift, protein kinase inhibition, in-gel kinase, and co-immunoprecipitation assays were used to address the role of Cbfa1 in mechanotransduction. RESULTS It was demonstrated that physiological amounts of mechanical deformation (stretching) directly up-regulate the expression and DNAbinding activity of Cbfa1 in human osteoblastic cells. This effect seems to be “fine-tuned” by stretch-triggered induction of distinct mitogen-activated protein kinase (MAPK) cascades. Importantly, it is shown that activated extracellular signal-regulated kinase (ERK) MAPK physically interacts and phosphorylates endogenous Cbfa1 in vivo, ultimately potentiating this transcription factor. CONCLUSIONS The findings of this study provide a molecular link between mechanostressing and stimulation of osteoblast differentiation. Elucidation of the specific modifiers and co-factors that operate in this mechanotranscription circuitry will contribute to a better understanding of mechanical load-induced bone formation which may set the basis for non-pharmacological intervention in bone loss pathologies.
Authors and Affiliations
P. ZIROS, A. ROJAS GIL, T. GEORGAKOPOULOS, I. HABEOS, D. KLETSAS, E. BASDRA
Keywords
Related Articles
- EP ID EP91279
- DOI -
- Views 52
- Downloads 0
Cabrera sign indicating old myocardial infarction
No abstract available
Dietary surveys: objectives, methodology<br /> and applications to the Greek population
In contemporary Greece, the face of malnutrition has changed. New deficiency syndromes have emerged (e.g. folic acid in relation to neural tube defects), but most nutrition-related disorders can now be attributed to nutr...
Writing scientific articles in health sciences
Research articles are the most common kind of publications in scientific journals and they are about the publication of studies that are conducted by health scientists. Almost all journals in health sciences have adopted...
Η επιδημιολογική φύση της ιατρικής επιστήμης<br />
AML, M5 type, -Beau Lines
A 35-year-old woman presented to the outpatient dep artment because of fever during the last fifteen days and symptoms from the upper respiratory tract. She was treated with trimethoprim/ sulphamethoxazole and the fe...