Tenascin-X is a large extracellular matrix protein of unknown function. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.

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The physical properties of the annulus fibrosus are critical to the intervertebral disc's biomechanical function; alterations with degeneration and aging can contribute directly to joint dysfunction and pain. A constitutive model that links the mechanical structure of the annulus to its material properties is important for many bioengineering purposes. To this end, we developed a strain energy function with separate terms to represent the matrix, the fibers, and the interactions between the constituents. Additionally, we measured the tensile and compressive stress-strain response of the annulus in the circumferential direction. We simultaneously applied the strain energy function to these new data and to data from a wide range of experimental protocols reported in the literature. By choosing experimental protocols that use an unloaded reference configuration, we developed a comprehensive formulation for the multiaxial annular elastic behavior. As a partial validation. this formulation predicted experimental results that were not included in model parameter specification. We anticipate that this constitutive formulation will be useful for computational simulations of the disc's biomechanical response and for elucidating structure-function relationships of the annulus fibrosus.

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