Efficacy of hyaluronic acid on intervertebral disc inflammation: An in vitro study using notochordal cell lines and human disc cells

Tatsuya Yamamoto, Satoshi Suzuki, Takeshi Fujii, Yuichiro Mima, Kota Watanabe, Morio Matsumoto, Masaya Nakamura, Nobuyuki Fujita

Research output: Contribution to journalArticlepeer-review

Abstract

Hyaluronic acid (HA) is widely recognized as a therapeutic target and currently used in medicine. However, HA metabolism during intervertebral disc degeneration (IVDD) has not been completely elucidated. This study aimed to evaluate the efficacy of HA on intervertebral disc (IVD) inflammation and identify the main molecules modulating HA degradation in IVDs. To assess HA function in IVD cells in vitro, we treated human disc cells and U-CH1-N cells, a notochordal nucleus pulposus cell line, with HA or hyaluronidase. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis showed that tumor necrosis factor alpha (TNF-α)-mediated induction of the expression of TNF-α and cyclooxygenase-2 (COX2) was clearly neutralized by HA treatment, and the expression of TNF-α and COX2 was significantly induced by hyaluronidase treatment in both cell types. Additionally, Western blot analysis showed that hyaluronidase-induced phosphorylation of p38 and Erk1/2, and that TNF-α-mediated phosphorylation of p38 and Erk1/2 was clearly reduced by HA addition. In degenerating human IVD samples, immunohistochemistry for hyaluronidase showed that the expression of hyaluronidases including HYAL1, HYAL2, and cell migration-inducing protein (CEMIP) tended to increase in accordance with IVDD. In particular, HYAL1 showed statistically significant differences. In vitro study also confirmed a similar phenomenon that TNF-α treatment increased both messenger RNA and protein expression in both cell types. Our results demonstrated that HA could potentially suppress IVDD by regulating p38 and Erk1/2 pathways, and that the expression of HYAL1 was correlated with IVDD progression. These findings indicated that HYAL1 would be a potential molecular target for suppressing IVDD by controlling HA metabolism.

Original languageEnglish
JournalJournal of Orthopaedic Research
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • cell migration-inducing protein
  • HYAL1
  • hyaluronic acid
  • hyaluronidase
  • intervertebral disc degeneration

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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