title: Nanomechanical phenotype of chondroadherin-null murine articular cartilage.
abstract: 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(-/-)). 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, Eind, 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(-/-) 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(-/-) 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.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Batista
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Hadi T
authors.initials: HT
authors.lastname: Nia
authors.affiliation: Department of Clinical Sciences, Lund University, 22184 Lund, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Önnerfjord
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, United States.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Cox
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Ortiz
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.affiliation: Department of Clinical Sciences, Lund University, 22184 Lund, Sweden.
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States. Electronic address: lh535@drexel.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*; D003094:Collagen / Q000378:metabolism; D004548:Elasticity; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D051379:Mice; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010641:Phenotype
chemical_list: D016326:Extracellular Matrix Proteins; C088980:chondroadherin; D003094:Collagen
keywords: Cartilage; Chondroadherin; Collagen; Murine model; Nanoindentation