Association between high plasma levels of hepatocyte growth factor and progression of radiographic damage in the joints of patients with rheumatoid arthritis

Arthritis Rheum. 2011 Mar;63(3):662-9. doi: 10.1002/art.30163.


Objective: Hepatocyte growth factor (HGF) and dickkopf-1 (Dkk-1) inhibit osteoblast differentiation. The present study was thus undertaken to investigate whether plasma levels of HGF and Dkk-1 are related to bone damage in patients with rheumatoid arthritis (RA).

Methods: RA patients with a disease duration of <4 years were followed up prospectively with collection of demographic, clinical, and radiographic data at study enrollment (1992) and after 1, 2, 5, and 10 years. Hand radiographs were scored according to the modified Sharp/van der Heijde score (SHS). Levels of HGF and Dkk-1 in stored plasma samples obtained from 136 patients at the time of enrollment were measured by enzyme-linked immunosorbent assay. Associations between cytokine levels and radiographic progression were examined by linear regression analysis.

Results: Patients with above-median levels of HGF at enrollment had a significantly greater change in the SHS after 1, 2, 5, and 10 years than did patients with below-median levels of HGF (P < 0.001, P = 0.006, P = 0.01, and P = 0.01, respectively). In an unadjusted analysis, baseline HGF levels predicted the severity of joint damage at all time points studied. After adjustment for other known predictors of radiographic progression, baseline HGF levels remained significantly associated with radiographic progression. Plasma levels of Dkk-1 at enrollment were not significantly associated with radiographic progression at any time point studied.

Conclusion: Plasma levels of HGF predict joint damage in RA, and this finding suggests that HGF plays a role in RA joint destruction. The role of HGF as a potential prognostic biomarker or target for treatment warrants further exploration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / pathology
  • Arthrography
  • Biomarkers / blood
  • Cell Differentiation / physiology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hepatocyte Growth Factor / blood*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Joints / pathology
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Osteoblasts / pathology
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies


  • Biomarkers
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Hepatocyte Growth Factor