Osteoprotegerin induction in response to microbial infection

Yasunari Takada,Koichi Matsuo

doi:10.1186/ar3668

Abstract

Osteoprotegeirn (OPG) is an endogenous decoy receptor for RANKL, which is a cytokine essential for osteoclast differentiation. Lipopolysaccharide (LPS) is known to induce osteoclast formation when injected onto calvaria in mice. Unexpectedly, we observed that mice injected with LPS up-regulate OPG and down-regulate RANKL levels in peripheral blood. In the present study, we examined whether OPG is induced by microbial infection of various kinds, and the sites and significance of OPG production in infected mice. Wild-type mice infected withSalmonella, Staphylococcus, Mycobacteriaor influenza virus showed increase in OPG levels in peripheral blood. We also found that the levels of OPG in serum of human patients infected with M. tuberculosis and M. avium were significantly increased. Moreover, injection of mice with LPS induced OPG production specifically in lymph nodes, especially in high endothelial venule (HEV)cells, but not in other organs. OPG production was suppressed in c-Fos-deficient mice and enhanced in Fra-1 transgenic mice, indicating that OPG production is regulated by AP-1 transcription factors. Loss of OPG in mice did not affect either their survival or Salmonella proliferation in spleen and liver after infection with virulent strains of Salmonella. Interestingly, however, when wild-type mice were infected with an avirulent Salmonella strain, which can induce OPG, osteoclast development was suppressed and bone mineral density was increased. These data reveal for the first time that lymph nodes protect bones from infection-induced bone loss through OPG production.

Highlights

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases
tumor necrosis factor (TNF) therapy and demyelinating event: A report indicates that adverse events such as the demyelinating lesion in the brain, optic neuritis, and neuropathy occurred after treatment with anti-TNF alpha therapy in collagen disease, and TNF antagonizing therapy showed worsening in a clinical trial with MS
Believing on the similarities of normal joints in humans and monkeys, we have employed a model of collagen-induced arthritis in Macaca fascicularis in an attempt to evaluate the histological alterations caused by such condition in the extracellular matrix of the articular cartilage

Summary

Introduction

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases. Acute Serum Amyloid A (A-SAA) is an acute phase protein strongly expressed in rheumatoid arthritis (RA) synovial tissue (ST) critically involved in regulating cell migration and angiogenesis These processes are dependent on downstream interactions between extracellular matrix and cytoskeletal components. Conclusions: These results indicate that Egr-1 contributes to IL-1mediated down-regulation of PPARg expression in OA chondrocytes and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases. Immune cell-derived microparticles (MPs) are present at increased amounts in synovial fluid of rheumatoid arthritis (RA) patients [1] and can activate disease-relevant signalling pathways in RA synovial fibroblasts (SF) [2,3].

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