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Applying a Three-dimensional Uniaxial Mechanical Stimulation Bioreactor System to Induce Tenogenic Differentiation of Tendon-Derived Stem Cells
Published on: August 1, 2020
Parameter-screened LED therapy targets STAT3/IL-6 axis to attenuate tendinopathy via dual modulation of inflammation
Peng Xia1, Tianxiang Fan1, Xiaoju Wang2
1Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.
Background:
Light-emitting diode (LED) therapy is a promising non-invasive approach for tendinopathy, yet clinical adoption is hindered by heterogeneous treatment parameters and undefined molecular mechanisms. The role of the Interleukin (IL)-6/signal transducer and activator of transcription 3(STAT3) signaling axis in LED-mediated tendon repair remains unexplored.
Objective:
This study aimed to screen effective LED parameters for mitigating tendinopathy by evaluating their effects on inflammation and extracellular matrix (ECM) synthesis in tenocytes, to preliminarily explore the role of the IL-6/STAT3 axis, and to validate the anti-inflammatory and pro-repair effects of selected parameters in a rodent model.
Methods:
Tenocytes from 8 week-old male Sprague-Dawley rat's Achilles's tendon were cultured and stimulated with IL-1β to model inflammatory tendinopathy. Cells underwent LED irradiation at varying wavelengths (625 nm, 810 nm, 940 nm) and energy densities. Cell viability was assessed via CCK-8 assay; expression of inflammatory markers (IL-6, Substance P (SP)), ECM components (type I collagen (COL1), type III collagen (COL3), and lubricin (PRG4) was quantified using qPCR, Western blot, and immunofluorescence to determine optimal LED parameters. STAT3 inhibition was applied to IL-1β-stimulated cells before LED treatment to probe STAT3's role. In vivo, collagenase-I was injected into rat Achilles tendons to induce tendinopathy, followed by LED therapy. Pain thresholds were measured using von Frey filaments, tendon histopathology was evaluated via Hematoxylin and Eosin (H&E) staining and modified Bonar scoring, and expression of COL1, COL3, IL-6, SP, and PRG4 was assessed by immunofluorescence and immunohistochemistry.
Results:
LED irradiation at 625 nm/52.8 J/cm2 markedly reduced IL-1β-induced IL-6 and SP expression, while 810 nm/39.6 J/cm2 and 940 nm/26.4 J/cm2 enhanced COL1 synthesis without affecting COL3 or PRG4 levels. Mechanistically, LED therapy restored IL-1β-suppressed STAT3 activation, an effect abrogated by STAT3 inhibition. In vivo, 625 nm and 940 nm LED treatments alleviated mechanical hyperalgesia in collagenase-I-induced tendinopathy, with 625 nm showing superior efficacy in reducing IL-6 and SP, enhancing COL1 deposition, and restoring tendon architecture.
Conclusions:
IL-1β disrupts tendon homeostasis by driving inflammation and ECM degradation. LED therapy at 625 nm/52.8 J/cm2 mitigates these effects, potentially by restoring STAT3 activity within the IL-6/STAT3 axis, thereby suppressing IL-6 expression.This provides a mechanistic foundation for refining LED-based tendinopathy treatments.
