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Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state.

Abstract：

OBJECTIVE:Mesenchymal stem cells (MSCs) are a promising cell type for the repair of damaged cartilage in osteoarthritis (OA). However, OA synovial fluid and factors secreted by synovium impede chondrogenic differentiation of MSCs, and the mechanism responsible for this effect remains unclear. In this study, we sought to investigate whether M1 and M2 synovial macrophages can contribute to the inhibition of MSC chondrogenesis. DESIGN:The constitution of synovial macrophage subsets was analysed by immunohistochemical staining of human OA synovium sections for CD86 (M1 marker) and CD206 (M2 marker). To assess the effect of synovial macrophages on chondrogenesis, collagen type II (COL2) and aggrecan (ACAN) gene expression were compared between MSCs undergoing chondrogenic differentiation in medium conditioned (CM) by human OA synovial explants, human synovial macrophages and fibroblasts, or peripheral blood derived primary human monocytes differentiated towards an M1 or M2 phenotype. RESULTS:OA synovium contained both M1 and M2 macrophages. Medium conditioned by synovial macrophages (CD45 + plastic adherent cells) down-regulated chondrogenic gene expression by MSCs. Additionally, CM of M1 polarised monocytes significantly decreased COL2 and ACAN gene expression by MSCs; this effect was not observed for treatment with CM of M2 polarised monocytes. CONCLUSION:MSC chondrogenesis is inhibited by OA synovium CM through factors secreted by synovial macrophages and our findings suggest that M1 polarised subsets are potential mediators of this anti-chondrogenic effect. Modulation of macrophage phenotype may serve as a beneficial strategy to maximise the potential of MSCs for efficient cartilage repair.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Fahy N,de Vries-van Melle ML,Lehmann J,Wei W,Grotenhuis N,Farrell E,van der Kraan PM,Murphy JM,Bastiaansen-Jenniskens YM,van Osch GJ

doi

10.1016/j.joca.2014.05.021

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

1167-75

issue

8

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(14)01100-5

journal_volume

22

pub_type

杂志文章

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