Dr. Meharra is deceased.
Accelerated, aging-dependent development of osteoarthritis in α1 integrin–deficient mice
Version of Record online: 7 OCT 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 10, pages 2873–2880, October 2003
How to Cite
Zemmyo, M., Meharra, E. J., Kühn, K., Creighton-Achermann, L. and Lotz, M. (2003), Accelerated, aging-dependent development of osteoarthritis in α1 integrin–deficient mice. Arthritis & Rheumatism, 48: 2873–2880. doi: 10.1002/art.11246
- Issue online: 7 OCT 2003
- Version of Record online: 7 OCT 2003
- Manuscript Accepted: 22 MAY 2003
- Manuscript Received: 5 NOV 2002
- NIH. Grant Number: AG-07996
Cell–matrix interactions regulate chondrocyte differentiation and survival. The α1β1 integrin is a major collagen receptor that is expressed on chondrocytes. Mice with targeted inactivation of the integrin α1 gene (α1-KO mice) provide a model that can be used to address the role of cell–matrix interactions in cartilage homeostasis and osteoarthritis (OA) pathogenesis.
Knee joints from α1-KO and wild-type (WT) BALB/c mice were harvested at ages 4–15 months. Knee joint sections were examined for inflammation, cartilage degradation, and loss of glycosaminoglycans (by Safranin O staining). Immunohistochemistry was performed to detect the distribution of α1 integrin, matrix metalloproteinases (MMPs), and chondrocyte apoptosis.
In WT mice, the α1 integrin subunit was detected in hypertrophic chondrocytes in the growth plate and in a subpopulation of cells in the deep zone of articular cartilage. There was a marked increase in α1-positive chondrocytes in the superficial and upper mid-zones in OA-affected areas in joints from old WT mice. The α1-KO mice showed more severe cartilage degradation, glycosaminoglycan depletion, and synovial hyperplasia as compared with the WT mice. MMP-2 and MMP-3 expression was increased in the OA-affected areas. In cartilage from α1-KO mice, the cellularity was reduced and the frequency of apoptotic cells was increased. These results suggest that the α1 integrin subunit is involved in the early remodeling process in OA cartilage.
Deficiency in the α1 integrin subunit is associated with an earlier deregulation of cartilage homeostasis and an accelerated, aging-dependent development of OA.