A joint study led by researchers from Xiamen University (XMU) and other institutions has identified a key mechanism by which sensory nerves regulate skeletal stem cells, shedding light on Alzheimer's-related bone loss.
The team was led by Professor Xu Ren of Xiamen University's School of Medicine, Chief Physician Huang Jianmin of Chenggong Hospital of Xiamen University, Professor Matthew B Greenblatt of Weill Cornell Medical College, and Professor Cheng Weinan of Shanghai Jiao Tong University Affiliated Sixth People's Hospital.
The study, titled "The p75 neurotrophin receptor controls the skeletal stem cell niche through sensory innervation", was published on Developmental Cell as a cover article.
Sensory nerves' neurotrophin receptor p75NTR was found to play a critical role in maintaining the skeletal stem cell (SSC) niche. Using mice engineered for sensory neuron–specific p75NTR deletion, the team observed reduced sensory innervation in bone, decreased SSC numbers, and significant bone loss.
Further experiments — including SSC transplantation, flow cytometry, immunofluorescence imaging, and molecular interventions — confirmed that p75NTR promotes SSC self-renewal and osteogenic differentiation by regulating the secretion of the protein SPP1 from sensory neurons.
Mechanistic analysis established the p75NTR-SPP1 signaling axis as a central pathway through which sensory nerves precisely modulate SSC function. The study also revealed that degeneration of bone-associated sensory nerves in Alzheimer's disease disrupts this axis, providing a direct explanation for AD-related reductions in bone mass.
