Sinus tarsi adipose tissue as a neuro-adipose niche in progressive collapsing foot deformity: neural innervation and stem cell properties.
4 affiliations
- 11st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
- 2Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy.
- 3Department of Orthopaedic Surgery, Foot and Ankle Division, Duke University School of Medicine, Durham, NC, United States.
- 4Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Abstract
The adipose tissue of the sinus tarsi has traditionally been viewed as a passive structure. Emerging evidence indicates it may function as a biologically active, innervated microenvironment contributing to proprioception and tissue homeostasis. As a rich source of mesenchymal stem cells, it also holds regenerative potential. However, its neural characteristics and stem cell properties remain underexplored. Adipose tissue samples were obtained from 20 patients undergoing surgery for symptomatic flatfoot deformity (progressive collapsing foot deformity - PCFD) and stratified by age (<18 vs. ≥ 18 years) and sex. Histology (H&E) and immunohistochemistry (S100, p75, PGP9.5) assessed neural elements, with quantitative analysis of immunopositive areas. Adipose-derived stem cells (ADSCs) were isolated and evaluated for viability (Alamar Blue) and osteogenic differentiation (gene expression: RUNX2, ALPL, COL1A1, BGLAP). Histology revealed preserved architecture with age-related stromal expansion, more pronounced in males ≥18 years. Neural markers are localized primarily to the stromal/vascular compartment, with p75 predominant across groups (p < 0.0001). Younger females showed highest neural marker expression; significant age-associated decline in patients with PCFD occurred in S100 and p75. ADSCs from younger females exhibited superior viability and early osteogenic marker expression, while aging correlated with reduced proliferation and a shift toward mature osteogenic phenotype, especially in males. The sinus tarsi harbors a dynamic neuro-adipose niche with age- and sex-dependent neural and stem cell features. This tissue may link proprioception with regenerative capacity and represents a promising autologous cell source for foot and ankle applications.
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BibTeX
@article{mazzotti2026sinus,
title = {{Sinus tarsi adipose tissue as a neuro-adipose niche in progressive collapsing foot deformity: neural innervation and stem cell properties.}},
author = {Antonio Mazzotti and Alberto Arceri and Cesar de Cesar Netto and Francesca Salamanna and Luca Cavazza and Gabriele Bilancia and Cesare Faldini and Gianluca Giavaresi and Francesca Veronesi},
journal = {Frontiers in medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1925286},
url = {https://europepmc.org/article/MED/42952849},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sinus tarsi adipose tissue as a neuro-adipose niche in progressive collapsing foot deformity: neural innervation and stem cell properties.
AU - Antonio Mazzotti
AU - Alberto Arceri
AU - Cesar de Cesar Netto
AU - Francesca Salamanna
AU - Luca Cavazza
AU - Gabriele Bilancia
AU - Cesare Faldini
AU - Gianluca Giavaresi
AU - Francesca Veronesi
PY - 2026
DA - 2026/10/14
JO - Frontiers in medicine
DO - 10.3389/fmed.2026.1925286
UR - https://europepmc.org/article/MED/42952849
AB - The adipose tissue of the sinus tarsi has traditionally been viewed as a passive structure. Emerging evidence indicates it may function as a biologically active, innervated microenvironment contributing to proprioception and tissue homeostasis. As a rich source of mesenchymal stem cells, it also holds regenerative potential. However, its neural characteristics and stem cell properties remain underexplored. Adipose tissue samples were obtained from 20 patients undergoing surgery for symptomatic flatfoot deformity (progressive collapsing foot deformity - PCFD) and stratified by age (<18 vs. ≥ 18 years) and sex. Histology (H&E) and immunohistochemistry (S100, p75, PGP9.5) assessed neural elements, with quantitative analysis of immunopositive areas. Adipose-derived stem cells (ADSCs) were isolated and evaluated for viability (Alamar Blue) and osteogenic differentiation (gene expression: RUNX2, ALPL, COL1A1, BGLAP). Histology revealed preserved architecture with age-related stromal expansion, more pronounced in males ≥18 years. Neural markers are localized primarily to the stromal/vascular compartment, with p75 predominant across groups (p < 0.0001). Younger females showed highest neural marker expression; significant age-associated decline in patients with PCFD occurred in S100 and p75. ADSCs from younger females exhibited superior viability and early osteogenic marker expression, while aging correlated with reduced proliferation and a shift toward mature osteogenic phenotype, especially in males. The sinus tarsi harbors a dynamic neuro-adipose niche with age- and sex-dependent neural and stem cell features. This tissue may link proprioception with regenerative capacity and represents a promising autologous cell source for foot and ankle applications.
SN - 2296-858X
ER -