Impact of diabetes mellitus on osteoarthritis: a scoping review on biomarkers

Abstract

Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs , ). Early management is important in order to avoid disability uphold quality of life (Ref. ). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. ). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs , , , ). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. ). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs , ).

Keywords: biomarkers; diabetes mellitus; inflammation; metabolism; osteoarthritis.

Figure 1.

PRISMA flow diagram of study selection.

Figure 2.

Postulated DM–OA biomarker pathway. An illustrated diagram with the proposed pathway for biomarkers which differentiates the diabetes-OA phenotype from the classical OA phenotype. The biomarkers with significant different in expression magnitude are listed according to sample origin. Red arrows and blue arrows indicate upregulated and downregulated OA with DM biomarker expression as compared with OA, respectively. **Indicates collagen type II expressed by human bone marrow-derived mesenchymal cells during chondrogenesis capacity experiment. Created with BioRender.com. ADAMTS4, a disintegrin and metalloproteinase with thrombospondin motif 4; ADAMTS5, a disintegrin and metalloproteinase with thrombospondin motif 5; AGEs, advanced glycation end-products; Akt, serine threonine kinase; ANGPTL2, angiopoietin-like protein 2; ASPN, asporin; ATF6, activating transcription factor 6; BGN, biglycan; BSG, basigin; C8A, C8 alpha chain N437; CD47, cluster of differentiation 47; COL1A1, collagen type 1 alpha 1 chain; COL6A2, collagen type VI alpha 1 chain; CTSD, cathepsin D; FBLN7, fibulin-7; FN1, fibronectin 1; GLUT-1, glucose transporter; GRP78, 78 kDa glucose-regulated protein; HbA1c, glycated haemoglobin; HIF-1α, hypoxia-inducible factor-1α; IGHM, immunoglobulin heavy constant mu; IL-6, interleukin-6; LC3, microtubule-associated protein 1A/1B-light chain 3; JCAD, junctional cadherin 5-associated protein; MG, methylglyoxal; MG-H1, free methylglyoxal-derived hydroimidazolone; MMP-1, matrix metalloproteinase-1; MMP-13, matrix metalloproteinase-13; NF-κB p65, RelA of nuclear factor kappa-light-chain-enhancer of activated B cells; PKC, protein kinase C; p-rpS6, phosphorylated ribosomal S6; RBP4, retinol binding protein 4; ROS, reactive oxygen species; SF COMP, synovial fluid cartilage oligomeric matrix protein; Smad3, SMAD family member 3; SPARC, secreted protein acidic and rich in cysteine/osteonectin; SOX9, SRY-box transcription factor 9; THBS3, thrombospondin 3; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2; TNC, tenascin C; TNF-α, tumour necrosis factor-alpha; TGFβRII, type II transforming growth factor-β receptor; VEGF, vascular endothelial growth factor.