Mechanical loading, such as caused by exercise, stimulates bone formation by osteoblasts and increases bone strength, but the mechanisms are poorly understood. Osteocytes reside in bone matrix, sense changes in mechanical load, and produce signals that alter bone formation by osteoblasts. We report that the ion channel Piezo1 is required for changes in gene expression induced by fluid shear stress in cultured osteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient to replicate the effects of fluid flow on osteocytes. Conditional deletion of Piezo1 in osteoblasts and osteocytes notably reduced bone mass and strength in mice. Conversely, administration of a Piezo1 agonist to adult mice increased bone mass, mimicking the effects of mechanical loading. These results demonstrate that Piezo1 is a mechanosensitive ion channel by which osteoblast lineage cells sense and respond to changes in mechanical load and identify a novel target for anabolic bone therapy.
Flexion instability after total knee arthroplasty (TKA) is caused by an increased flexion gap compared with extension gap. Patients present with recurrent effusions, subjective instability (especially going downstairs), quadriceps weakness, and diffuse periretinacular pain. Manual testing for laxity in flexion is commonly done to confirm a diagnosis, although testing positions and laxity grades are inconsistent. Nonsurgical treatment includes quadriceps strengthening and bracing treatment. The mainstays to surgical management of femoral instability involve increasing the posterior condylar offset, decreasing the tibial slope, raising the joint line in combination with a thicker polyethylene insert, and ensuring appropriate rotation of implants. Patient outcomes after revision TKA for flexion instability show the least amount of improvement when compared with revisions for other TKA failure etiologies. Future work is needed to unify reproducible diagnostic criteria. Advancements in biomechanical analysis with motion detection, isokinetic quadriceps strength testing, and computational modeling are needed to advance the collective understanding of this underappreciated failure mechanism.
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