Science: Oversensitive sensory neurons can lead to joint deformities

Researchers report that excessive mechanical sensation in neurons disrupts musculoskeletal development, leading to joint deformities such as joint contractures
.
Their study also demonstrates the notion that reducing this enhanced sensory neuron activity at a critical age (via Botox or a special diet) may be a viable way to treat certain musculoskeletal disorders in a non-invasive way
.

Distal joint contracture (DA) is a condition characterized by congenital joint deformities or contractures that usually limit movement of the hands and feet, and is estimated to affect one in every 3,000 people worldwide
.
Reducing symptoms usually requires invasive surgery
.
While genetic mutations associated with muscle and joint function are associated with DA, gain-of-function mutations in PIEZO2 – the primary mechanical sensor in sensory neurons – were found in patients with DA subtype 5 (DA5), which underlies
touch, proprioception, and other mechanosensory processes.
However, the mechanism by which PIEZO2 mutations lead to DA is unclear
.

Using mouse models, a team of researchers found that overexpression of the mutant Piezo2 function-acquired allele in proprioceptive neurons that disable muscles and tendons during the critical postnatal period during development can lead to joint contractures
.
These defects are not caused
when dysfunctional alleles are expressed in skeletal muscle, cartilage, or tendons.
According to Ma et al.
, dietary fatty acids commonly found in botulinum injections and fish can reduce joint and tendon defects
.

"The study by Ma et al.
provides exciting new insights into the mechanism by which DA occurs," Urich Müller wrote
in a related viewpoint.
"It is reassuring to find that expression of the function-acquired allele of Piezo2 does not cause DA symptoms in young adult mice
.
It narrows the window of time for potential therapeutic interventions, which may lead to lifelong improvement
in affected patients.
”