Miriam Weyers (Köln), Daniela Mählich (Köln), Charlotte Lorenz (Köln), Maren Dreiner (Köln), Thomas Li (Philadelphia, PA / US), Lin Han (Philadelphia, PA / US), Bent Brachvogel (Köln), Frank Zaucke (Frankfurt a. M.), Prof. Dr. Anja Niehoff (Köln)
Abstract-Text (inkl. Referenzen und Bildunterschriften)
Introduction
The mechanosensitive protein collagen IX (Col9) is located on the surface of collagen II-containing fibrils and involved in their interaction with each other and with other extracellular matrix (ECM) components1. Col9a1 deficient mice (Col9a1-/-) have an abnormal growth plate structure and an increased incidence of osteoarthritis (OA)2. Our study aimed to analyze the effect of forced running exercise on articular knee joint cartilage in Col9a1-/- mice.
Methods
12-week-old female wildtype C57BL/6N (WT) and Col9a1-/- mice2 were divided into control (CON) and exercise (EXE) groups (n=10/group/genotype). The EXE group was trained on a treadmill (20% incline, 20 m/min) five times a week for 40 min/day for 6 weeks. At an age of 18 weeks, knee cartilage degeneration was assessed using a modified OARSI score. Mechanical properties were analyzed by AFM-nanoindentation and the ECM was evaluated using immunohistochemistry and immunoblotting.
Results
None of the groups showed obvious cartilage degeneration. However, the articular cartilage of Col9a1-/- EXE mice had an increased elastic modulus while in the cartilage of Col9a1-/- CON mice MMP-13 staining intensity was significantly (p<0.05) increased compared to WT CON mice. Significantly (p<0.05) reduced COMP staining intensity and protein levels were detected in both Col9a1-/- groups compared to the WT groups. Interestingly, running exercise led to stronger reduced COMP staining intensity in Col9a1-/- EXE mice compared to Col9a1-/- CON mice.
Discussion
In Col9a1-/- mice, biomechanical and biochemical properties of articular cartilage are affected by running exercise. Increased MMP13 staining in Col9a1-/- CON mice might explain the increased susceptibility for OA and a first sign of beginning OA that is further enhanced in the EXE group indicated by more pronounced COMP loss.
1Zaucke F & Grässel S, Histol. Histopathol. 24: 1067-79, 2009
2Fässler R et al. Proc. Natl. Acad. Sci. U. S. A. 91: 5070-4, 1994