The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis

Han, Soo-Hong; Kim, Hyung Kyung; Jang, Yoon; Lee, Hyeon Hae; Rhie, Jeongbae; Han, Dong-Hun; Oh, Jongbeom; Lee, Soonchul

doi:10.1186/s12891-021-04067-1

Cited by 3 publications

(4 citation statements)

References 42 publications

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“… 23 , 33 However, the histological severity was not associated with SP and NGF expression level, which seems to be inconsistent with a recent report that documented that expression of SP evaluated by immunostaining was associated with histological severity of tendon degeneration in lateral epicondylitis. 22 This discrepancy is probably due to lack of samples with mild histopathologic changes which were included in the lateral epicondylitis study. As reported, microscopic pathology was typically much worse than macroscopic findings.…”

Section: Discussionmentioning

confidence: 99%

“…However, from an ethical point of view, it would be difficult to obtain age-matched normal LHBT samples and hence, the same idea was used when evaluating degenerative tendons in shoulder and elbow in previous studies. 21 , 22 Second, the number of patients and controls was small, though more patients were included than in previous similar studies with immunohistochemistry. 24 , 25 Third, not all consecutive cases underwent tenotomy or tenodesis of LHBT during ARCR, so possible selection bias existed.…”

Section: Discussionmentioning

confidence: 99%

“…To compare and validate the harvested LHBT samples, 1-cm fragment of healthy (non-degenerative) knee flexor tendon discarded during preparation of the graft was obtained from patients undergoing anterior cruciate ligament reconstruction. 21 , 22

Figure 3 Representative macroscopic view of the resected LHBT. Tissue sampling was done from worst macroscopic lesion at intra-articular ( A ) and intra-groove ( B ) area.…”

Section: Methodsmentioning

confidence: 99%

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Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear

Izumi¹,

Harada²,

Kajita³

et al. 2021

JPR

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Purpose Degenerative long head of biceps tendon (LHBT) has been recognized as a notable pain source in patients with rotator cuff tear (RCT). Tenotomy or tenodesis of LHBT is frequently indicated together with arthroscopic rotator cuff repair (ARCR) aiming for complete pain relief; however, it has not been fully investigated whether resected LHBT is really a source of pain. The purpose of this study was to investigate expression levels of pain-associated mediators in LHBT and its association with preoperative pain profiles. Methods Twenty-seven RCT patients who underwent ARCR with LHBT resection were included. Each LHBT was resected due to its abnormal arthroscopic findings including tenosynovitis, hypertrophy, and partial tear. Worst macroscopic lesion of the LHBT was obtained, and expression levels of substance P (SP) and nerve growth factor (NGF) were evaluated using enzyme-linked immunosorbent assay (ELISA). Ten healthy knee flexor tendons were analyzed as non-degenerative samples. Preoperatively, subjective shoulder pain VAS and pain duration were investigated. Conventional LHBT pain provocation tests (Speed, Yergason, O’Brien) were performed. Pressure pain threshold (PPT) of bilateral LHBT on the groove was recorded. Results Levels of SP and NGF expression were significantly higher compared with non-degenerative tendons (P<0.01). Shoulder pain VAS and pain duration were not directly associated with SP and NGF expression level. Patients with positive O’Brien test expressed greater SP than negative patients (P=0.001). Significant negative correlation between the PPT ratio (ipsilateral/contralateral) and SP expression level was observed (r=−0.453, P=0.034). Conclusion Greater expression of SP and NGF in degenerative LHBT supported our hypothesis that it would be a pain source in RCT patients. SP was likely to be expressed highly in patients with localized pressure pain hypersensitivity and positive O’Brien test (ie, altered mechanistic pain profile of LHBT), which may help when considering simultaneous LHBT resection during ARCR. Clinical Registration UMIN000023943.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Figure 3 Representative macroscopic view of the resected LHBT. Tissue sampling was done from worst macroscopic lesion at intra-articular ( A ) and intra-groove ( B ) area.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear

Izumi¹,

Harada²,

Kajita³

et al. 2021

JPR

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“…However, it also plays an important role in the pathogenesis of tendinopathy as excessive stimulation leads to neo-innervation together with tissue breakdown and degeneration. The release of neuropeptides, such as substance P, stimulates the degranulation of mast cells, with the subsequent release of agents that modulate many cellular activities within the matrix ( Scott and Bahr, 2009 ; Han et al, 2021 ; Millar et al, 2021 ). Despite the numerous advances in characterizing the pathogenesis of tendon disorders, a gold standard clinical treatment remains somewhat elusive ( Millar et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Human Tendon Stem/Progenitor Cell Features and Functionality Are Highly Influenced by in vitro Culture Conditions

Orfei

Bowles

Kouroupis

et al. 2021

Front. Bioeng. Biotechnol.

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Our understanding of tendon biology continues to evolve, thus leading to opportunities for developing novel, evidence-based effective therapies for the treatment of tendon disorders. Implementing the knowledge of tendon stem/progenitor cells (TSPCs) and assessing their potential in enhancing tendon repair could fill an important gap in this regard. We described different molecular and phenotypic profiles of TSPCs modulated by culture density, as well as their multipotency and secretory activities. Moreover, in the same experimental setting, we evaluated for different responses to inflammatory stimuli mediated by TNFα and IFNγ. We also preliminarily investigated their immunomodulatory activity and their role in regulating degradation of substance P. Our findings indicated that TSPCs cultured at low density (LD) exhibited cobblestone morphology and a reduced propensity to differentiate. A distinctive immunophenotypic profile was also observed with high secretory and promising immunomodulatory responses when primed with TNFα and IFNγ. In contrast, TSPCs cultured at high density (HD) showed a more elongated fibroblast-like morphology, a greater adipogenic differentiation potential, and a higher expression of tendon-related genes with respect to LD. Finally, HD TSPCs showed immunomodulatory potential when primed with TNFα and IFNγ, which was slightly lower than that shown by LD. A shift from low to high culture density during TSPC expansion demonstrated intermediate features confirming the cellular adaptability of TSPCs. Taken together, these experiments allowed us to identify relevant differences in TSPCs based on culture conditions. This ability of TSPCs to acquire distinguished morphology, phenotype, gene expression profile, and functional response advances our current understanding of tendons at a cellular level and suggests responsivity to cues in their in situ microenvironment.

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Predictive Neuromarker Patterns for Calcification Metaplasia in Early Tendon Healing

Faydaver,

Festinese,

Di Giacinto

et al. 2024

Veterinary Sciences

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Unsuccessful tendon healing leads to fibrosis and occasionally calcification. In these metaplastic drifts, the mouse AT preclinical injury model represents a robust experimental setting for studying tendon calcifications. Previously, calcium deposits were found in about 30% of tendons after 28 days post-injury. Although a neuromediated healing process has previously been documented, the expression patterns of NF200, NGF, NPY, GAL, and CGRP in mouse AT and their roles in metaplastic calcific repair remain to be explored. This study included a spatiotemporal analysis of these neuromarkers during the inflammatory phase (7 days p.i.) and the proliferative/early-remodelling phase (28 days p.i.). While the inflammatory phase is characterised by NF200 and CGRP upregulation, in the 28 days p.i., the non-calcified tendons (n = 16/24) showed overall NGF, NPY, GAL, and CGRP upregulation (compared to 7 days post-injury) and a return of NF200 expression to values similar to pre-injury. Presenting a different picture, in calcified tendons (n = 8), NF200 persisted at high levels, while NGF and NPY significantly increased, resulting in a higher NPY/CGRP ratio. Therefore, high levels of NF200 and imbalance between vasoconstrictive (NPY) and vasodilatory (CGRP) neuromarkers may be indicative of calcification. Tendon cells contributed to the synthesis of neuromarkers, suggesting that their neuro-autocrine/paracrine role is exerted by coordinating growth factors, cytokines, and neuropeptides. These findings offer insights into the neurobiological mechanisms of early tendon healing and identify new neuromarker profiles predictive of tendon healing outcomes.

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The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis

Cited by 3 publications

References 42 publications

Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear

Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear

Human Tendon Stem/Progenitor Cell Features and Functionality Are Highly Influenced by in vitro Culture Conditions

Predictive Neuromarker Patterns for Calcification Metaplasia in Early Tendon Healing

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