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Acquired heterotopic ossifications (HO) arising as a result of various traumas, including injury or surgical interventions, often result in pain and loss of motion. Though triggers for HO have been identified, the cellular source of these heterotopic lesions as well as the underlying mechanisms that drive the formation of acquired HO remain poorly understood, and treatment options, including preventative treatments, remain limited. Here, we explore the cellular source of HO and a possible underlying mechanism for their spontaneous osteogenic differentiation. We demonstrate that HO lesions arise from tissue-resident PDGFRα+ fibro/adipogenic progenitors (FAPs) in skeletal muscle and not from circulating bone marrow-derived progenitors. Further, we show that accumulation of these cells in the tissue after damage due to alterations in the inflammatory environment can result in activation of their inherent osteogenic potential. This work suggests a mechanism by which an altered inflammatory cell and FAP interactions can lead to the formation of HO after injury and presents potential targets for therapeutics in acquired HO.

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An analytical model is developed in this paper which relates the major component of micro-EHL pressure responses to lubricant properties, roughness geometry, contact load, velocity, and slide-to-roll ratio. Analyses are then conducted showing the effects of system parameters on this micro-EHL pressure. For a Newtonian lubricant with an exponential pressure-viscosity law, this pressure would be large unless the contact practically operates right at pure rolling. The magnitude of the pressure rippling is largely independent of the slide-to-roll ratio, and smaller wavelength components of the surface roughness generate larger micro-EHL pressures. With less dramatic pressure-viscosity enhancement such as the two-slope model, the micro-EHL pressure is generally smaller and sensitive to the slide-to-roll ratio, larger with higher sliding in the contact. Furthermore, this pressure-viscosity model yields a micro-EHL pressure that becomes vanishingly small corresponding to sufficiently small wavelength components of the roughness. For a shear-thinning non-Newtonian lubricant, such as the Eyring model, with an exponential pressure-viscosity law, substantially less micro-EHL pressure rippling is generally developed than its Newtonian counterpart. While the pressure rippling is insensitive of the slide-to-roll ratio like its Newtonian counterpart, it vanishes corresponding to sufficiently small wavelength components of the roughness. The analyses revealed that a key factor resulting in a smaller micro-EHL pressure with the two-slope model or the Eyring model is the lower viscosity or shear-thinned effective viscosity in the loaded region of the contact. Since EHL traction is proportional to this viscosity, contacts lubricated with oils exhibiting higher traction behavior would develop larger micro-EHL pressures and thus would be more vulnerable to fatigue failure.