Nanomechanical phenotype of chondroadherin-null murine articular cartilage

• Main Authors: Batista, Michael A. (Contributor), Cox, Karen A. (Author), Ortiz, Christine (Contributor), Grodzinsky, Alan J. (Contributor), Han, Lin (Contributor), Tavakoli Nia, Hadi (Contributor), Onnerfjord, Patrik (Author), Heinegard, Dick (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Massachusetts Institute of Technology. Department of Materials Science and Engineering (Contributor), Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2014-08-22T15:25:42Z.
• Subjects: Article
• Online Access: Get fulltext

Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD[superscript −/−]). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈ 70-80% reduction in the indentation modulus, E[subscript ind], of the superficial zone knee cartilage of 11 weeks, 4 months and 1 year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD[superscript −/−] knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD[superscript −/−] cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice.
National Science Foundation (U.S.) (Grant CMMI-0758651)
National Institutes of Health (U.S.) (Grant AR60331)
United States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (National Security Science and Engineering Faculty Fellowship Grant N00244-09-1-0064)
Shriners Hospital for Children