Dynamic compressive strain influences chondrogenic gene expression in human periosteal cells: A case study

Physical stimuli play a crucial role in skeletogenesis and osteochondral repair and regeneration. Although the periosteum and periosteum-derived cells offer considerable therapeutic potential, the molecular mechanisms that control their differentiation are still not fully understood. As an initial case study, this work explores the hypothesis that dynamic compression might selectively enhance chondrogenic and/or osteogenic differentiation in human periosteal cells from two donors. Donor derived human periosteal cells were expanded in monolayer culture before seeding in 3% (w/v) agarose constructs. The ability of this in vitro   culture model to support cell viability, chondrogenesis, and mechanotransduction was optimised. The time course of early chondrogenic differentiation was assessed by real time RT-PCR of mRNA expression levels for bone and cartilage specific gene markers. Intermittent dynamic compression (1 Hz, 15% strain) was applied to constructs, in the presence or absence of 10 ng/ml TGF-β3β3, for up to 4 days. The combined effect of TGF-β3β3 and compressive loading on the expression levels of the Sox-9, Runx-2, ALP, Collagen X, and collagen type I genes was donor dependent. A synergistic effect was noted only in donor two, with peak mRNA expression levels at 24 h, particularly Sox-9 which increased 59.0-fold. These findings suggest that the interactions between mechanical stimuli and TGF-ββ signalling may be an important mechanotransduction pathway for human periosteal cells and that, importantly, this cellular mechanosensitivity varies between donors.

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► Mechanical strain may enhance differentiation in human periosteal cells.
► TGF-β3β3 with compressive loading had a synergistic effect on the expression of several genes.
► Interactions between mechanical stimuli and TGF-ββ signalling for human periosteal cells.
► Cellular mechanosensitivity varies between donors.