Focal adhesion kinase is important for fluid shear stress-induced mechanotransduction in osteoblasts

Suzanne R L Young, Rita Gerard-O'Riley, Jae Beom Kim, Fredrick Pavalko

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Mechanical loading of bone is important for maintenance of bone mass and structural stability of the skeleton. When bone is mechanically loaded, movement of fluid within the spaces surrounding bone cells generates fluid shear stress (FSS) that stimulates osteoblasts, resulting in enhanced anabolic activity. The mechanisms by which osteoblasts convert the external stimulation of FSS into biochemical changes, a process known as mechanotransduction, remain poorly understood. Focal adhesions are prime candidates for transducing external stimuli. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase found in focal adhesions, may play a key role in mechanotransduction, although its function has not been directly examined in osteoblasts. We examined the role of FAK in osteoblast mechanotransduction using short interfering RNA (siRNA), overexpression of a dominant negative FAK, and FAK-/- osteoblasts to disrupt FAK function in calvarial osteoblasts. Osteoblasts were subjected to varying periods oscillatory fluid flow (OFF) from 5 min to 4 h, and several physiologically important readouts of mechanotransduction were analyzed including: extracellular signal-related kinase 1/2 phosphorylation, upregulation of c-fos, cyclooxygenase-2, and osteopontin, and release of prostaglandin E2. Osteoblasts with disrupted FAK signaling exhibited severely impaired mechanical responses in all endpoints examined. These data indicate the importance of FAK for both short and lone periods of FSS-induced mechanotransduction in osteoblasts.

Original languageEnglish
Pages (from-to)411-424
Number of pages14
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume24
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Osteoblasts
Bone and Bones
Focal Adhesions
Osteopontin
Cyclooxygenase 2
Dinoprostone
Skeleton
Protein-Tyrosine Kinases
Small Interfering RNA
Phosphotransferases
Up-Regulation
Maintenance
Phosphorylation

Keywords

  • Integrins
  • Mechanical loading
  • Osteoblasts
  • Osteopontin
  • Stress/strain

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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abstract = "Mechanical loading of bone is important for maintenance of bone mass and structural stability of the skeleton. When bone is mechanically loaded, movement of fluid within the spaces surrounding bone cells generates fluid shear stress (FSS) that stimulates osteoblasts, resulting in enhanced anabolic activity. The mechanisms by which osteoblasts convert the external stimulation of FSS into biochemical changes, a process known as mechanotransduction, remain poorly understood. Focal adhesions are prime candidates for transducing external stimuli. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase found in focal adhesions, may play a key role in mechanotransduction, although its function has not been directly examined in osteoblasts. We examined the role of FAK in osteoblast mechanotransduction using short interfering RNA (siRNA), overexpression of a dominant negative FAK, and FAK-/- osteoblasts to disrupt FAK function in calvarial osteoblasts. Osteoblasts were subjected to varying periods oscillatory fluid flow (OFF) from 5 min to 4 h, and several physiologically important readouts of mechanotransduction were analyzed including: extracellular signal-related kinase 1/2 phosphorylation, upregulation of c-fos, cyclooxygenase-2, and osteopontin, and release of prostaglandin E2. Osteoblasts with disrupted FAK signaling exhibited severely impaired mechanical responses in all endpoints examined. These data indicate the importance of FAK for both short and lone periods of FSS-induced mechanotransduction in osteoblasts.",
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