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Oversensitive sensory neurons can cause joint deformities

Excessive mechanosensation in the neurons that enable the sense of one’s limbs in space can disrupt musculoskeletal development and cause…

By Staff , in Orthopedics , at January 19, 2023 Tags:

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Excessive mechanosensation in the neurons that enable the sense of one’s limbs in space can disrupt musculoskeletal development and cause joint deformities like arthrogryposis, researchers report. Their study also provides proof of concept that reducing this heightened sensory neuronal activity (via Botox or special diet) during a critical age could be a viable way to treat some musculoskeletal conditions in a non-invasive manner. Distal arthrogryposis (DA) is a disorder characterized by congenital joint deformities, or contractures, that often restrict movement in the hands and feet and is estimated to afflict roughly one in 3,000 individuals worldwide. Alleviating the symptoms often requires invasive surgeries. Although mutations in genes associated with muscle and joint function have been linked to DA, gain-of-function mutations in PIEZO2 – a principal mechanosensor in sensory neurons that underlies touch sensation, proprioception, and other mechanosensory processes – have been found in patients with DA subtype 5 (DA5). However, the mechanism by which PIEZO2 mutations cause DA is unknown. Using a mouse model, Shang Ma and colleagues found that over-expression of the mutant Piezo2 gain-of-function allele in proprioceptive neurons that enervate muscles and tendons during a critical postnatal period during development can cause joint contracture. These defects were not caused when the dysfunctional allele was expressed in skeletal muscles, cartilage, or tendons. According to Ma et al., Botox injection and a dietary fatty acid commonly found in fish reduced joint and tendon defects. “The study by Ma et al. provides exciting new insights into the mechanisms that cause DA,” writes Urich Müller in a related Perspective. “Finding that expression of the gain-of-function allele of Piezo2 in young adult mice does not cause DA symptoms is reassuring. It narrows down a time window for potential therapeutic intervention that could lead to lifelong improvement for the affected patients.”

Staff
The team at The Medical Dispatch

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