In pathological states such as osteoarthritis, the complex metabolic balance of cartilage is disrupted leading to a loss in the integrity and biomechanical function of cartilage1. Osteoarthritis affects more than 20 million Americans, costing the United States economy over $60 billion yearly2. Risk factors for osteoarthritis include age, excessive joint loading, and joint injury. Tissue engineering offers a potential solution for the replacement of diseased and/or damaged cartilage3,4. Unfortunately, plentiful donor cell populations are difficult to assemble, as chondrocytes have a well characterized lack of expansion potential5. Mesenchymal progenitor cells (MPCs) offer an alternative with a high expansion potential capable of supplying large quantities of cells. Using an immature bovine model, the chondrogenic differentiation of articular chondrocytes (BACs) and bone marrow stromal cells was found to be scaffold, media and mechanical stimulation dependent. Mechanisms modulating mechanotransduction in BACs were explored, including ion-channel and TGF-β signaling.
TGF-β signaling participated in the response of articular chondrocytes to dynamic compressive loading, as well as enhanced the chondrogenesis of bovine BMSCs, through interactions between loading and TGF-β/Smad signaling. Also, dynamic loading altered gene expression, matrix synthesis rates and intracellular phosphorylation for bovine BMSCs. However the response of the cells to dynamic loading depends on both media supplementation and the duration of unloaded culture. These studies establish signaling through the TGF-beta pathway as a mechanotransduction pathway for chondrocytes and chondroprogenitors in 3D culture.
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