HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways

Cell Commun Signal. 2022 Aug 30;20(1):132. doi: 10.1186/s12964-022-00943-y.

Abstract

Osteoarthritis (OA) is an age-related chronic degenerative joint disease where the main characteristics include progressive degeneration of cartilage, varying degrees of synovitis, and periarticular osteogenesis. However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in poor clinical treatment effect. Recently, glucose metabolism changes provide a new perspective on the pathogenesis of OA. Under the stimulation of external environment, the metabolic pathway of chondrocytes tends to change from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Previous studies have demonstrated that glycolysis of synovial tissue is increased in OA. The hexokinase (HK) is the first rate limiting enzyme in aerobic glycolysis, participating and catalyzing the main pathway of glucose utilization. An isoform of HKs, HK2 is considered to be a key regulator of glucose metabolism, promotes the transformation of glycolysis from OXPHOS to aerobic glycolysis. Moreover, the expression level of HK2 in OA synovial tissue (FLS) was higher than that in control group, which indicated the potential therapeutic effect of HK2 in OA. However, there is no summary to help us understand the potential therapeutic role of glucose metabolism in OA. Therefore, this review focuses on the properties of HK2 and existing research concerning HK2 and OA. We also highlight the potential role and mechanism of HK2 in OA. Video abstract.

Keywords: Chondrocyte; Glycolysis; Hexokinase 2; Metabolism; Osteoarthritis.

Publication types

  • Review
  • Video-Audio Media
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glucose / metabolism
  • Glycolysis*
  • Hexokinase / metabolism*
  • Humans
  • Osteoarthritis* / metabolism
  • Synovial Membrane / pathology

Substances

  • HK2 protein, human
  • Hexokinase
  • Glucose