PMID- 32317146 OWN - NLM STAT- MEDLINE DCOM- 20210922 LR - 20220302 IS - 1436-2023 (Electronic) IS - 0949-2658 (Print) IS - 0949-2658 (Linking) VI - 26 IP - 2 DP - 2021 Mar TI - Effect of a monocyte chemoattractant protein-1 synthesis inhibitor on fibroblasts from patients with carpal tunnel syndrome. PG - 295-299 LID - S0949-2658(20)30081-6 [pii] LID - 10.1016/j.jos.2020.03.010 [doi] AB - BACKGROUND: Carpal Tunnel Syndrome (CTS) is an idiopathic fibrotic disorder. Fibrosis in the subsynovial connective tissues (SSCT) of CTS and many other fibrotic diseases is mediated by Transforming growth factor beta (TGF-beta). Recently monocyte chemoattractant protein-1 (MCP-1) a cytokine involved in cellular recruitment has been suggested to regulate TGF-beta activity. It is related to the onset of diseases which are caused by fibrosis, such as idiopathic pulmonary fibrosis, renal fibrosis, and systemic scleroderma. In this study, we evaluated the effect of the MCP-1 synthesis inhibitor, Bindarit, on primary cultures of fibroblasts from the SSCT of five CTS patients. METHODS: Fibroblasts were treated with Bindarit (10 muM, 50 muM, 100 muM, or 300 muM). Responses to inhibitors were evaluated by regulation of CTS fibrosis-associated genes, fibrosis gene array and Smad luciferase reporter assay. We also assessed the combination effect of Bindarit and SD208, a TGF-beta receptor type 1 inhibitor on TGF-beta signaling. RESULTS: Collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 expression were significantly down-regulated by Bindarit (300 muM) compared to vehicle control. In the fibrosis array, expression of inhibin beta E chain precursor (INHBE), beta actin (ACTB), endothelin 1 (EDN1) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) were significantly down-regulated, and integrin beta-3 (ITGB3) was significantly up-regulated by Bindarit (300 muM). Smad signal transduction activation was significantly down-regulated by Bindarit (300 muM) and/or SD208 (1 muM) with TGF-beta1 compared to vehicle control with TGF-beta1. CONCLUSIONS: These results suggest that Bindarit in combination with SD208 may be beneficial as medical therapy for the SSCT fibrosis associated with CTS. CI - Copyright (c) 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved. FAU - Yamanaka, Yoshiaki AU - Yamanaka Y AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Gingery, Anne AU - Gingery A AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Oki, Gosuke AU - Oki G AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Yang, Tai-Hua AU - Yang TH AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Zhao, Chunfeng AU - Zhao C AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Amadio, Peter C AU - Amadio PC AD - Department of Orthopedic Surgery, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Electronic address: pamadio@mayo.edu. LA - eng GR - F32 AR063596/AR/NIAMS NIH HHS/United States GR - R01 AR049823/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20200419 PL - Japan TA - J Orthop Sci JT - Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association JID - 9604934 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Collagen Type III) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - *Carpal Tunnel Syndrome/drug therapy MH - *Chemokine CCL2/antagonists & inhibitors MH - Collagen Type III MH - Fibroblasts MH - Fibrosis MH - Humans MH - Transforming Growth Factor beta MH - Transforming Growth Factor beta1 PMC - PMC7572818 MID - NIHMS1581431 COIS- Declaration of Competing Interest None. EDAT- 2020/04/23 06:00 MHDA- 2021/09/23 06:00 PMCR- 2022/03/01 CRDT- 2020/04/23 06:00 PHST- 2019/10/15 00:00 [received] PHST- 2020/02/03 00:00 [revised] PHST- 2020/03/05 00:00 [accepted] PHST- 2020/04/23 06:00 [pubmed] PHST- 2021/09/23 06:00 [medline] PHST- 2020/04/23 06:00 [entrez] PHST- 2022/03/01 00:00 [pmc-release] AID - S0949-2658(20)30081-6 [pii] AID - 10.1016/j.jos.2020.03.010 [doi] PST - ppublish SO - J Orthop Sci. 2021 Mar;26(2):295-299. doi: 10.1016/j.jos.2020.03.010. Epub 2020 Apr 19.