Abstract
Local joint inflammation plays an important role in the pathogenesis of temporomandibular joint (TMJ) osteoarthrosis (TMJOA). Yohimbine, an alpha-2 adrenergic receptor antagonist, possesses anti-inflammatory properties; however, the ability of Yohimbine to protect against TMJOA-associated chondrocyte inflammation remains unclear. We conducted in vitro and in vivo analyses to investigate whether Yohimbine could ameliorate TMJOA-induced chondrocyte inflammation and to elucidate the mechanisms involved. Chondrocytes of TMJOA mice were stimulated with interleukin (IL)-1β or noradrenaline (NE), and the resulting production of inflammation-related factors was evaluated in the presence or absence of Yohimbine. Furthermore, two TMJOA mouse models were treated with Yohimbine and the therapeutic effect was quantified. NE (10−6 M) triggered inflammatory cytokine secretion by TMJ chondrocytes, and Yohimbine suppressed IL-1β- or NE-induced IL-6 upregulation in TMJ chondrocytes with the nuclear factor (NF)–κB pathway inhibition. Yohimbine also ameliorated cartilage destruction in the TMJOA models. Interestingly, αmpT, a tyrosine hydroxylase inhibitor, reversed the effects of Yohimbine by activating the NF-κB pathway. Collectively, these findings show that Yohimbine ameliorated TMJ chondrocyte inflammation and the suppression of NF-κB pathway contributes to this effect.
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Abbreviations
- ANOVA:
-
Analysis of variance
- AR:
-
Adrenergic receptor
- cAMP:
-
Cyclic adenosine monophosphate
- CBA:
-
Cytometric bead array
- CT:
-
Computed tomography
- DAB :
-
3,30-Diaminobenzidine
- DMEM:
-
Dulbecco’s modified Eagle medium
- DMSO:
-
Dimethyl sulfoxide
- HE:
-
Hematoxylin and eosin
- Ig:
-
Immunoglobulin
- IL:
-
Interleukin
- LPS:
-
Lipopolysaccharide
- MSC:
-
Mesenchymal stem cell
- NE:
-
Norepinephrine
- OA:
-
Osteoarthritis
- PBS:
-
Phosphate-buffered saline
- TH:
-
Tyrosine hydroxylase
- TMD:
-
Temporomandibular disease
- TMJ:
-
Temporomandibular joint
- TMJOA:
-
Temporomandibular joint osteoarthrosis
- TNF:
-
Tumor necrosis factor
- WB:
-
Western blot
- Yoh:
-
Yohimbine
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Funding
This work was supported by the Natural Science Foundation of Guangdong Province, China (Grant No: 2018A030313726) and the Science and Technology Planning Project of Guangdong Province, China (Grant No: 2015A030302019).
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Conceptualization, Farong Ou and Jiadong Sun; methodology, Yihuan Huang; software, Dongxiao Tang; validation, Dongxiao Tang; formal analysis, Rongsheng Zeng; investigation, Jiadong Sun; resources, Kai Su; data curation, Farong Ou; writing—original draft preparation, Farong Ou; writing—review and editing, Kai Su; visualization, Yihuan Huang and Dongxiao Tang; supervision, Guiqing Liao; project administration, Guiqing Liao; funding acquisition, Kai Su, Yiqing He. All authors have read and agreed to the published version of the manuscript.
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Ou, F., Huang, Y., Sun, J. et al. Yohimbine Ameliorates Temporomandibular Joint Chondrocyte Inflammation with Suppression of NF-κB Pathway. Inflammation 44, 80–90 (2021). https://doi.org/10.1007/s10753-020-01310-0
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DOI: https://doi.org/10.1007/s10753-020-01310-0