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THU0071 The role of transforming growth factor b (tgfb) in bone metabolism in rheumatoid arthritis
  1. S Drynda1,
  2. G Pap2,
  3. C Kühne1,
  4. W Neumann2,
  5. J Kekow1
  1. 1Clinic of Rheumatology
  2. 2Clinic of Orthopedics, Otto-Von-Guericke-University, Magdeburg, Germany

Abstract

Background TGFb can be found in high concentrations in bone matrix. It is produced by osteoclasts and osteoblasts and is considered as a local regulator of bone metabolism. TGFb is an important factor in the coupling of bone resorption and formation. TGFb induces synthesis of matrix proteins and inhibits matrix degradation by downregulation of MMPs and may thereby counteract pro-resorptive cytokines such as IL-1, IL-6 and TNFa. The role of the different isoforms of TGFb is not yet fully understood. In rheumatoid arthritis elevated plasma levels of TGFb1 and TGFb2 have been described.

Objectives It was the aim of this study to determine the role of TGFb for bone metabolism in RA.

Methods 36 RA patients and 55 patients with osteoarthritis (OA) were included in this study. Total TGFbs in plasma samples and bone extracts were determined after transient acidification applying three isoform specific ELISAs.

Bone mineral density was measured by dexa-scan (Hologic QDR 4500W) at the lumbar spine and femoral neck. Diagnosis of osteoporosis and osteopenia, respectively, was defined according to the WHO osteoporosis criteria from 1994.

Results Plasma concentrations of TGFb1 were significantly elevated in RA patients compared to OA patients (7.31 ± 1.10 ng/ml vs. 4.11 ± 0.35 ng/ml, mean ± SEM, p < 0.05), the other two isoforms did not show differences. Concentrations of TGFbs isolated from bone were strongly associated with each other with a predominance of TGFb1 >TGFb2 >TGFb3.

Although the concentrations of TGFb1 in bone were slightly elevated in the RA group compared to the OA group (0.49 ± 0.07 vs. 0.38 ± 0.04 ng/mg bone powder) no significant differences were found. No association was found for TGFb levels in peripheral blood and in the corresponding bone extracts. The highest concentrations of TGFb1 from bone were found in patients with reduced bone mineral density. A strong negative correlation was found between bone TGFb1 levels and T-score values (r = -0.479, p = 0.002).

Conclusion The finding of elevated TGFb1 concentrations in bone samples from patients with osteoporosis is in contrast to earlier findings, which suggest a protective effect of TGFb against matrix degradation. In this study the highest concentrations of extractable TGFb1 were found in RA patients with high bone loss. Thus it may be possible that more proinflammatory features of TGFb are important in bone metabolism, such as the stimulation of IL-6 as described for primary rat osteoblasts. The quantification of total TGFb in the bone matrix may not sufficiently describe the situation in vivo. Post translational processes like activation of the latent TGFb and its availability determine the biological effects of this regulatory cytokine.

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