Article Text

02.14 Small ubiquitin related modifier-1 (sumo-1) regulates osteoclast differentiation
  1. Svetlana Frank1,
  2. David JJ de Gorter1,
  3. Daniel Umlauf1,
  4. Olli A Jänne2,
  5. Berno Dankbar1,
  6. Thomas Pap1
  1. 1Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Muenster, Germany
  2. 2Univ Helsinki, Inst Biomed Physiol, Biomedicum, Helsinki, Finland


Background Rheumatoid arthritis is a common autoimmune disease characterised by the hyperplastic transformation of synovium, its infiltration with γ inflammatory cells and by stimulation of bone resorption through osteoclast activation leading to joint destruction. Posttranslational modification by SUMOylation has been described for various proteins and is involved in a wide variety of cellular processes, including protein localization and stability, transcriptional regulation, cell survival and death. Here, we investigated the role of SUMO-1 in osteoclastogenesis and studied the skeletal phenotype of SUMO-1-/- mice.

Materials and methods The skeletal phenotype of 8-week old SUMO-1-/- and wild- type (WT) mice was investigated by µCT-analysis and by van Kossa and TRAP stainings. For in vitro experiments, bone marrow-derived macrophages (BMMs) were isolated from SUMO-1-/- and WT mice, and differentiated into osteoclasts in presence of M-CSF and RANKL. Osteoclast differentiation was characterised by TRAP staining and by real-time PCR analysis of osteoclast marker genes. Activation of p38 and p44/42 MAPK as well as NF-κB signalling was investigated by western blotting. The osteoclast resorption capacity was determined using a calcium phosphate bone resorption assay. Cell motility was analysed by live cell imaging.

Results SUMO-1-/- mice demonstrated 20% higher trabecular bone volume compared with WT mice. Moreover, trabecular thickness was increased and trabecular separation was decreased in SUMO-1-/- mice. In addition, SUMO-1-/- mice display a significant reduction in osteoclasts. Of note, SUMO-1 loss was associated with impaired in vitro osteoclast differentiation and resorption capacity. Expression of DC-STAMP, cathepsin K and integrin ß3 was decreased in SUMO-1-/- osteoclasts compared to WT osteoclasts. However, no differences in activation of p38 and p44/42 MAPK as well as the NF-κB signalling pathway in BMMs and osteoclasts of SUMO-1-/- and WT mice was observed. Conversely, cell migration and fusion seemed to be affected in SUMO-1-/- osteoclasts.

Conclusions We found that SUMO-1-/- mice have a higher bone mass owing to a decreased number of functional osteoclasts. Our data suggest that SUMO-1 is involved in the regulation of bone mass by osteoclast formation and activity, and therefore may be an interesting target for treating diseases associated with bone loss.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.