High molecular weight hyaluronan protects cartilage from degradation by inhibiting aggrecanase expression

Takashi Ohtsuki, Keiichi Asano, Junko Inagaki, Akira Shinaoka, Kanae Kumagishi-Shinaoka, Mehmet Z. Cilek, Omer F. Hatipoglu, Toshitaka Oohashi, Keiichiro Nishida, Issei Komatsubara, Satoshi Hirohata

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hyaluronan (HA) is an extracellular matrix (ECM) component of articular cartilage and has been used to treat patients with osteoarthritis (OA). A disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs) play an important role in cartilage degradation in OA. We have previously reported that ADAMTS4 and ADAMTS9 were induced by cytokine stimulation. However, the effect of HA on the cytokine-inducible ADAMTS9 has never been investigated. Moreover, it is unclear whether HA protects cartilage by suppressing aggrecan degradation. Here, we examined the effects of HA on ADAMTS expression in vitro and on cartilage degradation in vivo. ADAMTS9 expression was higher than that of the other aggrecanases (ADAMTS4 and 5) in human chondrocytes, chondrocytic cells, and rat cartilage. ADAMTS4 and 9 mRNA levels were upregulated in cytokine-stimulated chondrocytes and chondrocytic cells. Pre-incubation with HA significantly inhibited ADAMTS9 mRNA expression in cytokine-stimulated cells. In a rat OA model, Adamts5 and 9 mRNA levels were transiently increased after surgery; intra-articular HA injections attenuated the induction of Adamts5 and 9 mRNA. HA also blocked aggrecan cleavage by aggrecanase in OA rats in a molecular size-dependent manner. These results demonstrate that HA attenuates induced aggrecanases expression in OA and thereby protects articular cartilage degradation by this enzyme. Our findings provide insight into the molecular basis for the beneficial effects of HA in OA.

Original languageEnglish
Pages (from-to)3247-3255
Number of pages9
JournalJournal of Orthopaedic Research
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • aggrecan
  • chondrocyte
  • hyaluronic acid
  • metalloproteinase

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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