Dr. Seol and Mr. McCabe contributed equally to this work.
Chondrogenic progenitor cells respond to cartilage injury
Article first published online: 27 OCT 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 11, pages 3626–3637, November 2012
How to Cite
Seol, D., McCabe, D. J., Choe, H., Zheng, H., Yu, Y., Jang, K., Walter, M. W., Lehman, A. D., Ding, L., Buckwalter, J. A. and Martin, J. A. (2012), Chondrogenic progenitor cells respond to cartilage injury. Arthritis & Rheumatism, 64: 3626–3637. doi: 10.1002/art.34613
- Issue published online: 27 OCT 2012
- Article first published online: 27 OCT 2012
- Accepted manuscript online: 6 JUL 2012 09:56AM EST
- Manuscript Accepted: 26 JUN 2012
- Manuscript Received: 30 SEP 2011
- US Department of Defense. Grant Number: W81XWH-10-1-0702a
- World Arthrosis Organization
Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to posttraumatic osteoarthritis. However, we observed 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. The aim of this study was to assess our hypothesis that the migrating cell population included chondrogenic progenitor cells that were drawn to injured cartilage by alarmins.
Osteochondral explants obtained 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 medium, dead cell debris, and high mobility group box chromosomal protein 1 (HMGB-1).
Migrating cells were highly clonogenic and multipotent and expressed markers associated with chondrogenic progenitor cells. Compared with chondrocytes, these cells overexpressed genes involved in proliferation and migration and underexpressed cartilage matrix genes. They were more active than chondrocytes in chemotaxis assays and responded to cell lysates, conditioned medium, and HMGB-1. Glycyrrhizin, a chelator of HMGB-1 and a blocking antibody to 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.
Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitor cells, in part via HMGB-1 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.