Skip to main content
Journal cover image

Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.

Publication ,  Conference
Xie, JW; Wang, Y; Xiao, K; Xu, H; Luo, ZY; Li, L; Pei, FX; Kraus, VB; Huang, ZY
Published in: Osteoarthritis Cartilage
July 2021

OBJECTIVE: Macrophages play an important part in the pathogenesis of osteoarthritis (OA). Our objective was to determine the effects of α-defensin-1 on macrophage polarization and consequently OA. METHODS: OA synovial tissue and synovial fluid were assessed for the presence of M1 (CD68+CD16+CD206-) and M2 (CD68+CD206+CD16-) macrophages by flow cytometry. M0, M1, and M2 macrophages were co-cultured with OA chondrocytes to determine their influence on chondrogenic phenotype. Polarization of THP-1 activated monocytes from M1 to M2 in response to α-defensin-1 was evaluated by flow cytometry, RT-PCR and RNA sequencing. Effects of intra-articular α-defensin-1 in vivo were evaluated in a rat meniscal/ligamentous injury (MLI) model. RESULTS: The quantity of M1 exceeded M2 polarized macrophages in human OA synovial tissue (mean difference 26.1% [13.6-38.6%], P < 0.001) and fluid (mean difference 10.5% [5.0-16.1%], P = 0.003). M1 to M2 polarization in vitro was most effectively promoted with 10 ng/mL α-defensin-1. Compared with untreated macrophages, the α-defensin-1 polarized macrophages modified co-cultured OA chondrocytes from a pro-catabolic state to a pro-anabolic (regenerative-like) state based on expression of COL2A1, ACN, MMP3, MMP13 and ADAMTS5. Intra-articular α-defensin-1 decreased severity of cartilage damage and synovitis in the MLI rat model. RNAseq analyses suggested insulin and Toll-like receptor signaling pathways in the chondroprotective α-defensin-1 mechanism of action. CONCLUSION: α-defensin-1 promotes M1 to M2 macrophage polarization in vitro, has beneficial effects on chondrocytes indirectly via M2 macrophage polarization, and attenuates the severity of OA in vivo, suggesting it might be a candidate treatment for OA.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

July 2021

Volume

29

Issue

7

Start / End Page

1048 / 1059

Location

England

Related Subject Headings

  • alpha-Defensins
  • Synovial Membrane
  • Synovial Fluid
  • Osteoarthritis
  • Macrophages
  • Humans
  • Coculture Techniques
  • Cell Polarity
  • Arthritis & Rheumatology
  • Anti-Infective Agents
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xie, J. W., Wang, Y., Xiao, K., Xu, H., Luo, Z. Y., Li, L., … Huang, Z. Y. (2021). Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization. In Osteoarthritis Cartilage (Vol. 29, pp. 1048–1059). England. https://doi.org/10.1016/j.joca.2021.04.006
Xie, J. W., Y. Wang, K. Xiao, H. Xu, Z. Y. Luo, L. Li, F. X. Pei, V. B. Kraus, and Z. Y. Huang. “Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.” In Osteoarthritis Cartilage, 29:1048–59, 2021. https://doi.org/10.1016/j.joca.2021.04.006.
Xie JW, Wang Y, Xiao K, Xu H, Luo ZY, Li L, et al. Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization. In: Osteoarthritis Cartilage. 2021. p. 1048–59.
Xie, J. W., et al. “Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.Osteoarthritis Cartilage, vol. 29, no. 7, 2021, pp. 1048–59. Pubmed, doi:10.1016/j.joca.2021.04.006.
Xie JW, Wang Y, Xiao K, Xu H, Luo ZY, Li L, Pei FX, Kraus VB, Huang ZY. Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization. Osteoarthritis Cartilage. 2021. p. 1048–1059.
Journal cover image

Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

July 2021

Volume

29

Issue

7

Start / End Page

1048 / 1059

Location

England

Related Subject Headings

  • alpha-Defensins
  • Synovial Membrane
  • Synovial Fluid
  • Osteoarthritis
  • Macrophages
  • Humans
  • Coculture Techniques
  • Cell Polarity
  • Arthritis & Rheumatology
  • Anti-Infective Agents