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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
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- 1 - 13 (13page)
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The objective of this study was to investigate the regulatory effects of TGF-β1 on CCL3/4 expression and inflammation-related pain during intervertebral disc degeneration (IVDD). TGF-β1 and CCL3/4 expression patterns in different degenerative human nucleus pulposus (NP) tissues were measured by qPCR and immunohistochemistry (IHC), and the effects of TGF-β1 on CCL3/4 expression were measured by qPCR, ELISA and immunofluorescence. The roles of NF-κB and MAPK in TGF-β1-mediated CCL3/4 promoter activity were studied using siRNAs, western blotting and qPCR. After establishing an IVDD rat model in vivo, we administered intradiscal injections of TGF-β1. The effects of TGF-β1 on IVDD were determined by MRI and histological analyses, and the effects of TGF-β1 on dorsal root ganglion (DRG) inflammation and pain development were determined by IHC staining and pain-behavior testing, respectively. TGF-β1 and CCL3/4 expression was elevated in degenerative NP tissue. CCL4 expression was significantly inhibited by TGF-β1 treatment. Pharmacological inhibition or siRNA knockdown of the ERK1/2 signaling attenuated TGF-β1-mediated suppression of CCL4 expression. In vivo, TGF-β1 injection inhibited the development of degenerative features in the IVDD model. Moreover, TGF-β1 prevented the inflammatory response and pain development.
The results of this study show that TGF-β1 downregulates CCL4 expression through ERK1/2 signaling activation in NP cells.
Furthermore, TGF-β1 can prevent degenerative processes, inhibit inflammatory responses in the DRG and prevent pain development in the IVDD rat model. The results of this study indicate that TGF-β1 may represent a therapeutic target for the control of inflammation-related pain associated with IVDD.
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참고문헌 (23)
참고문헌 신청
Balague F / 2012 / Non-specific low back pain / Lancet 379 : 482 ~ 491
Freemont AJ / 2009 / The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain / Rheumatology 48 : 5 ~ 10
Gerard C / 2001 / Chemokines and disease / Nat Immunol 2 : 108 ~ 115
Haringman JJ / 2004 / Chemokines in joint disease : the key to inflammation? / Ann Rheum Dis 63 : 1186 ~ 1194
Kiguchi N / 2010 / CC-chemokine MIP-1alpha in the spinal cord contributes to nerve injury-induced neuropathic pain / Neurosci Lett 484 : 17 ~ 21
Freemont AJ / 2009 / The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain / Rheumatology 48 : 5 ~ 10
Gerard C / 2001 / Chemokines and disease / Nat Immunol 2 : 108 ~ 115
Haringman JJ / 2004 / Chemokines in joint disease : the key to inflammation? / Ann Rheum Dis 63 : 1186 ~ 1194
Kiguchi N / 2010 / CC-chemokine MIP-1alpha in the spinal cord contributes to nerve injury-induced neuropathic pain / Neurosci Lett 484 : 17 ~ 21
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