scholarly journals NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seungyong Lee ◽  
Charles Hwang ◽  
Simone Marini ◽  
Robert J. Tower ◽  
Qizhi Qin ◽  
...  

AbstractPain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation.

1994 ◽  
Vol 07 (04) ◽  
pp. 180-182
Author(s):  
N. Gofton ◽  
Joanne Cockshutt

The AO wire passer can be used as an effective guide for passage of obstetrical saw wire for osteotomy. Use of the wire saw and passer reduces soft tissue trauma by minimizing tissue dissection, and promoting positioning of the saw in close contact with the bone.


1992 ◽  
Vol 8 (04) ◽  
pp. 233-241 ◽  
Author(s):  
Fred Stucker ◽  
Denis Hoasjoe

2000 ◽  
Vol 48 (3) ◽  
pp. 479-483 ◽  
Author(s):  
Patricia S. Landry ◽  
Andrew A. Marino ◽  
Kalia K. Sadasivan ◽  
James A. Albright

1978 ◽  
Vol 10 (6) ◽  
pp. 404-414 ◽  
Author(s):  
M. Silberschmid ◽  
C. Lund ◽  
K. Szczepanski ◽  
S. Lyager

1974 ◽  
Vol 6 (4) ◽  
pp. 233-246 ◽  
Author(s):  
J. Sandegård ◽  
J. Nolte ◽  
D.H. Lewis ◽  
T. Seeman

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0015 ◽  
Author(s):  
Nicholas Bellas ◽  
Carl Cirino ◽  
Mark Cote ◽  
Vinayak Sathe ◽  
Lauren Geaney

Category: Other Introduction/Purpose: Patient reported outcome measures serve as an invaluable tool in both the clinical and research setting to monitor a patient’s condition and efficacy of treatments over time. We aim to validate the Single Assessment Numeric Evaluation (SANE) score for disorders of the lower extremity using the revised Foot Function Index (rFFI) as a reference. The rFFI is a validated 34-question survey tool utilized in the evaluation of patients with foot and ankle related pathology [1-4], while the SANE score consists of a patient’s single numerical rating of the status of their extremity [5]. Given its ease of use and prior validation with shoulder pathology, the SANE score has potential as a practical and effective outcome measure in foot and ankle pathology. Methods: Patient age, sex, visit diagnosis by ICD-10 code, SANE score, and FFI score were collected retrospectively from 218 initial patient encounters between January 2015 through July 2017. Patients were included if they were 18 years and older presenting for outpatient evaluation to the University of Connecticut Foot and Ankle Orthopedic Department. Patients were excluded if they had incomplete SANE or rFFI data. The rFFI is a 34-question survey with subscales including pain (7 questions), stiffness (7 questions), activity limitation (3 questions), difficulty (11 questions), and social issues (6 questions). Results of the two scores were compared using the Pearson or Spearman correlation coefficients with correlation defined as excellent (>0.7), excellent-good (0.61-0.7), good (0.4-0.6), or poor (0.2-0.39) [6]. Diagnoses were categorized into 9 subgroups that were analyzed including: forefoot, plantar fasciitis, arthritis, deformity, fracture, tendinitis, OCD, soft tissue trauma and “other”. Results: The SANE score had good correlation with the overall rFFI score (r=0.51, p<0.001). When comparing the SANE score to the rFFI subscores, there was good correlation with pain (r=0.42, p<0.001), good correlation with stiffness (r=0.44, p<0.001), poor correlation with activity (r=0.36, p<0.001), good correlation with difficulty (r=0.52, p<0.001), and poor correlation with social issues (r=0.39, p<0.001). Sub-analysis showed an excellent to good correlation between SANE and rFFI score for forefoot pathology (r=0.67, p<0.001), “other” pathologies (r=0.65, p<0.001), and plantar fasciitis (r=0.63, p<0.016), good correlation for arthritis (r=0.49, p<0.038), deformity (r=0.60, p<0.010), fracture (r=0.50, p<0.004), and tendinitis (r=0.47, p<0.017), and no significant correlation for OCD of the talus (r=0.56, p<0.145) and soft tissue trauma (r=0.19, p<0.319). Conclusion: The SANE score demonstrates good correlation with the rFFI overall. However, its correlation varies depending on the subscore of the rFFI and the presenting pathology of the patient. The SANE score correlates best with the rFFI pain, stiffness, and difficulty subscore, and poorly with activity and social issues. In addition, the SANE score correlates best with forefoot pathologies, plantar fasciitis, and “other” pathologies but does not correlate with patients presenting for OCD of the talus or soft tissue trauma.


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