Document Detail

Chondrogenic progenitor cells respond to cartilage injury.
MedLine Citation:
PMID:  22777600     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to post-traumatic osteoarthritis. However, we found that nonviable areas in cartilage injured by blunt impact were repopulated within 7-14 days by cells that appeared to migrate from the surrounding matrix. We hypothesized that the migrating population included chondrogenic progenitor cells drawn to injured cartilage by alarmins. METHODS: Osteochondral explants from mature cattle were injured by blunt impact or scratching, resulting in localized chondrocyte death. Injured sites were serially imaged by confocal microscopy and migrating cells were evaluated for chondrogenic progenitor characteristics. Chemotaxis assays were used to measure the responses to chemokines, injury-conditioned media, dead cell debris, and high mobility group box 1 (HMGB1). RESULTS: Migrating cells were highly clonogenic, multipotent, and expressed markers associated with chondrogenic progenitors. Compared with chondrocytes, these cells over-expressed genes involved in proliferation and migration, and under-expressed cartilage matrix genes. They were more active in chemotaxis assays than chondrocytes and responded to cell lysates, conditioned medium, and HMGB1. Glycyrrhizin, a chelator of HMGB1 and a blocking antibody to the receptor for advanced glycation end products (RAGE) inhibited responses to cell debris and conditioned medium, and reduced the numbers of migrating cells on injured explants. CONCLUSION: Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitors in part via HMGB1 release and RAGE-mediated chemotaxis. Their repopulation of the matrix could promote the repair of chondral damage that might otherwise contribute to progressive cartilage loss.
Dongrim Seol; Daniel J McCabe; Hyeonghun Choe; Hongjun Zheng; Yin Yu; Keewoong Jang; Morgan W Walter; Abigail D Lehman; Lei Ding; Joseph A Buckwalter; James A Martin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-6
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Department of Orthopaedics and Rehabilitation, The University of Iowa, Iowa City, IA.
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