Evaluation of the post-treatment anti-inflammatory capacity of osteoarthritic chondrocytes: An in vitro study using baicalein

Chang-Chin Wu; Yi-Ru Chen; Dai-Hua Lu; Li-Ho Hsu; Kai-Chiang Yang; Shoichiro Sumi

doi:10.1016/j.reth.2020.02.002

Evaluation of the post-treatment anti-inflammatory capacity of osteoarthritic chondrocytes: An in vitro study using baicalein

Regen Ther. 2020 Feb 24:14:177-183. doi: 10.1016/j.reth.2020.02.002. eCollection 2020 Jun.

Authors

Chang-Chin Wu^{1

2

3}, Yi-Ru Chen^{1

4}, Dai-Hua Lu⁴, Li-Ho Hsu^{1

2}, Kai-Chiang Yang^{4

5}, Shoichiro Sumi⁵

Affiliations

¹ Department of Orthopedics, En Chu Kong Hospital, New Taipei City, 23702, Taiwan.
² Department of Orthopedics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10002, Taiwan.
³ Departments of Biomedical Engineering, Yuanpei University of Medical Technology, Hsinchu City 300, Taiwan.
⁴ School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
⁵ Laboratory of Organ and Tissue Reconstruction, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.

Abstract

Introduction: Targeting inflammatory cascades is considered a promising way to prevent knee osteoarthritis (OA) progression. In terms of down-regulating the expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and matrix metalloproteinases (MMPs), pre-treatment with the flavonoid baicalein reportedly protects articular chondrocytes against the cytotoxicity of IL-1β. However, the benefits of post-treatment baicalein on osteoarthritic chondrocytes are not fully elucidated.

Methods: In this study, primary human chondrocytes were stimulated with IL-1β prior to baicalein application to evaluate the therapeutic effect of post-treatment.

Results: Post-treatment baicalein alleviated cell death and partially restored mitochondrial viability, while the senescence-associated secretory phenotype was not improved in IL-1β-stimulated chondrocytes. Post-treatment baicalein down-regulated the expressions of IL-1β, tumor necrosis factor-alpha, MMP-3, MMP-9, and MMP-13 mRNA as well as the protein production in stimulated cells. Even so, the levels of these factors were relative higher than those in un-treated chondrocytes. Moreover, iNOS, IL-6, IL-8, and COL1A1 expressions were consistently high, and IL-10 protein synthesis steadily increased in IL-1β-treated chondrocytes under baicalein treated status. Moreover, Western blot analyses showed that post-treatment baicalein suppressed nuclear factor kappa-light-chain-enhancer of activated B cells and p50 production while downstream cyclooxygenase-2 was still highly expressed.

Conclusion: Baicalein post-treatment to osteoarthritic chondrocytes had a minor benefit to the homeostasis of cartilaginous extracellular matrix.

Keywords: Baicalein; Interleukin-10; Matrix metalloproteinase; Osteoarthritis; Pro-inflammatory cytokine.