Beta1 integrins mediate mechanosensitive signaling pathways in osteocytes.
Integrins are cell-substrate adhesion proteins that initiate intracellular signaling and may serve as mechanosensors in bone. MLO-Y4 cells were stably transfected with a dominant negative form of the beta(1) integrin subunit (beta(1)DN) containing the transmembrane domain and cytoplasmic tail of beta(1) integrin. Cells expressing beta(1)DN had reduced vinculin localization to focal contacts but no change in intracellular actin organization. When exposed to oscillatory fluid flow, beta(1)DN cells exhibited a significant reduction in the upregulation of cyclooxygenase-2 gene expression and prostaglandin E(2) release. Similarly, the ratio of receptor activator of NF-kappaB ligand mRNA to osteoprotegerin mRNA decreased significantly after exposure to fluid flow in control cells but not in beta(1)DN cells. Interfering with integrin signaling did not affect mechanically induced intracellular calcium mobilization. These data suggest that integrins may initiate the cellular response of osteocytes to dynamic fluid flow and may serve as mechanosensitive molecules in bone.
Litzenberger
Julie B
JB
Department of Veterans Affairs, Bone and Joint Rehabilitation Center, Palo Alto, CA, USA. Julitzy@gmail.com
Kim
Jae-Beom
JB
Tummala
Padmaja
P
Jacobs
Christopher R
CR
D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D008954:Models, Biological; D010011:Osteocytes / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010812:Physical Stimulation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011673:Pulsatile Flow / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D019012:Integrin beta1; D010446:Peptide Fragments; D021122:Protein Subunits; D002118:Calcium