Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients.
Arthroplasty
Collagen type I
Fibrosis
Knee
Lysyl hydroxylase
Minoxidil
Osteoarthritis
Pyridinoline
Synovial fibroblasts
Synovium
Journal
Journal of experimental orthopaedics
ISSN: 2197-1153
Titre abrégé: J Exp Orthop
Pays: Germany
ID NLM: 101653750
Informations de publication
Date de publication:
21 Aug 2023
21 Aug 2023
Historique:
received:
16
03
2023
accepted:
09
08
2023
medline:
22
8
2023
pubmed:
22
8
2023
entrez:
21
8
2023
Statut:
epublish
Résumé
Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b histology or culture. Protein and RNA were purified from fibrotic FSCs after 8 days with or without 0.5 µM MXD and/or 4 ng/mL of TGFβ1. COL1 and Pyd protein concentrations from ELISA and expression of Col1a1, Acta2, and Plod2 genes by qPCR were compared by parametric tests with α = 0.05. Histological LH2b expression corresponded to SFb severity. MXD attenuated COL1 output in KOA FSCs but only in the absence of TGFβ1 and consistently decreased Pyd under all conditions with significant downregulation of Plod2 but minimal alterations to Col1a1 and Acta2 transcripts. MXD is an attractive candidate for local antifibrotic pharmacotherapy for SFb by compromising the integrity of newly formed fibrous deposits by FSCs during KOA and following arthroplasty. Targeted antifibrotic supplementation could improve physical therapy and arthroscopic lysis strategies aimed at breaking down joint scarring. However, the effect of MXD on other joint-specific TGFβ1-mediated processes or non-fibrotic components requires further investigation.
Identifiants
pubmed: 37605092
doi: 10.1186/s40634-023-00650-8
pii: 10.1186/s40634-023-00650-8
pmc: PMC10441905
doi:
Types de publication
Journal Article
Langues
eng
Pagination
84Subventions
Organisme : NIGMS NIH HHS
ID : U54 GM104940
Pays : United States
Informations de copyright
© 2023. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).
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