Oncostatin M and Mechanotransduction in Bone Cells
The study described herein investigated the relationship between Oncostatin M, the osteoblast cytoskeleton, and matrix compliance. Osteoblast cells are responsible for the formation of bone. Oncostatin M (OSM) is an inflammatory cytokine that has been shown to increase mineralization by osteoblast cultures in vitro; this increased mineralization represents a stiffening of the extra cellular matrix (ECM). The stiffness or elasticity of tissue, also known as matrix compliance, is a mechanical property of the cell’s external environment. Changes in the external mechanical environment elucidate responses in the cytoskeleton that in turn facilitate changes in cellular biochemistry. This process, known as mechanotransduction, can modulate gene expression, and subsequently, proliferation and differentiation. Therefore, the relationship between OSM, matrix compliance, and the osteoblast cytoskeleton may have consequences in diseases involving reduced osteoblast proliferation and activity, such as osteoporosis.
MC3T3 E-1 cells are an immortalized murine osteoblast cell line used in this study. To mimic physiologically representative matrix compliance, MC3T3 cells were cultured on polyacrylamide hydrogels of varying stiffness; this property can be tuned by varying the ratio of acrylamide to bis-acrylamide. Cells were cultured across a range of elasticity (25-40 kPa) in the presence and absence of OSM, and their cytoskeletal morphology was visualized via phalloidin staining and confocal microscopy. In order to evaluate the effects of OSM and matrix compliance on cytoskeletal dynamics, cellular shape, total filamentous actin, and actin fiber geometry were compared across conditions.