Low-Intensity Pulsed Ultrasound Promotes Chondrogenic Progenitor Cell Migration via Focal Adhesion Kinase Pathway

Kee W Jang; Lei Ding; Dongrim Seol; Tae-Hong Lim; Joseph A Buckwalter; James A Martin

doi:10.1016/j.ultrasmedbio.2013.12.007

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Low-Intensity Pulsed Ultrasound Promotes Chondrogenic Progenitor Cell Migration via Focal Adhesion Kinase Pathway

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Low-Intensity Pulsed Ultrasound Promotes Chondrogenic Progenitor Cell Migration via Focal Adhesion Kinase Pathway

Kee W Jang, Lei Ding, Dongrim Seol, Tae-Hong Lim, Joseph A Buckwalter and James A Martin

Ultrasound in medicine & biology, Vol.40(6), pp.1177-1186

06/2014

DOI: 10.1016/j.ultrasmedbio.2013.12.007

PMCID: PMC4034572

PMID: 24612644

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Abstract

Low-intensity pulsed ultrasound (LIPUS) has been studied frequently for its beneficial effects on the repair of injured articular cartilage. We hypothesized that these effects are due to stimulation of chondrogenic progenitor cell (CPC) migration toward injured areas of cartilage through focal adhesion kinase (FAK) activation. CPC chemotaxis in bluntly injured osteochondral explants was examined by confocal microscopy, and migratory activity of cultured CPCs was measured in transwell and monolayer scratch assays. FAK activation by LIPUS was analyzed in cultured CPCs by Western blot. LIPUS effects were compared with the effects of two known chemotactic factors: N-formyl-methionyl-leucyl-phenylalanine (fMLF) and high-mobility group box 1 (HMGB1) protein. LIPUS significantly enhanced CPC migration on explants and in cell culture assays. Phosphorylation of FAK at the kinase domain (Tyr 576/577) was maximized by 5 min of exposure to LIPUS at a dose of 27.5 mW/cm2 and frequency of 3.5 MHz. Treatment with fMLF, but not HMBG1, enhanced FAK activation to a degree similar to that of LIPUS, but neither fMLF nor HMGB1 enhanced the LIPUS effect. LIPUS-induced CPC migration was blocked by suppressing FAK phosphorylation with a Src family kinase inhibitor that blocks FAK phosphorylation. Our results imply that LIPUS might be used to promote cartilage healing by inducing the migration of CPCs to injured sites, which could delay or prevent the onset of post-traumatic osteoarthritis.

Post-traumatic osteoarthritis

Focal adhesion kinase

Articular cartilage

Cell migration

Low-intensity pulsed ultrasound

Details

Title: Subtitle: Low-Intensity Pulsed Ultrasound Promotes Chondrogenic Progenitor Cell Migration via Focal Adhesion Kinase Pathway
Creators: Kee W Jang - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
Lei Ding - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
Dongrim Seol - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
Tae-Hong Lim - Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
Joseph A Buckwalter - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
James A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Ultrasound in medicine & biology, Vol.40(6), pp.1177-1186
DOI: 10.1016/j.ultrasmedbio.2013.12.007
PMID: 24612644
PMCID: PMC4034572
NLM abbreviation: Ultrasound Med Biol
ISSN: 0301-5629
eISSN: 1879-291X
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: P50 AR055533
Language: English
Date published: 06/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Orthodontics; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
Record Identifier: 9984040355502771

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