Synovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation

Sean Xiang Zhang, Jane E. Aubin, Tae Hwan Kim, Ursula Payne, Basil Chiu, Robert D. Inman

Research output: Contribution to journalArticle

Abstract

The mechanisms whereby arthritogenic organisms may induce cartilage and bone erosions in infection-triggered arthritis remain unknown. In this study, we asked whether an arthritogenic organism could contribute to osteoclast differentiation and activation through regulation of the receptor activator of NF-ê ligand (RANKL) in synovial fibroblasts. Rat synovial fibroblasts were infected in vitro with Salmonella enterica serovar Typhimurium and monitored over time. The expression of RANKL in resting and infected synovial fibroblasts was quantified by reverse transcription-PCR and Western blotting. Osteoclast progenitors, isolated from femurs of 8-week-old rats and cultured in the presence of macrophage colony-stimulating factor, were cocultured with either infected or noninfected synovial fibroblasts for 2 to 4 days. Differentiation and maturation of osteoclasts were determined by morphology and tartrate-resistant acid phosphatase (TRAP) staining and by a bone resorption bioassay. RANKL expression was undetectable in resting synovial fibroblasts but was dose-dependently upregulated in cells after Salmonella infection. Osteoprotegerin was constitutively expressed by synovial fibroblasts and was not upregulated by infection. Further, we observed the formation of multinucleated TRAP-positive cells and formation of bone resorption pits in cocultures of bone marrow-derived osteoclast precursors with synovial fibroblasts infected with Salmonella but not with heat-killed Salmonella or noninfected cells. Arthritogenic bacteria may alter bone structure via synovial fibroblast intermediaries, since infected synovial fibroblasts (i) upregulate RANKL expression and (ii) enhance osteoclast precursor maturation into multinucleated, TRAP-positive, bone-resorbing, osteoclast-like cells. These data provide a link between infection and osteoclastogenesis. A better understanding of infection-mediated osteoclast differentiation and activation may provide new therapeutic strategies for inflammatory joint disease.

Original languageEnglish (US)
Pages (from-to)7183-7189
Number of pages7
JournalInfection and Immunity
Volume72
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

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Salmonella enterica
Osteoclasts
Fibroblasts
Bone Resorption
Infection
Bone and Bones
Salmonella
Serogroup
Osteoprotegerin
Macrophage Colony-Stimulating Factor
Salmonella Infections
Joint Diseases
Coculture Techniques
Osteogenesis
Biological Assay
Femur
Reverse Transcription
Arthritis
Cartilage
Up-Regulation

ASJC Scopus subject areas

  • Immunology

Cite this

Synovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation. / Zhang, Sean Xiang; Aubin, Jane E.; Kim, Tae Hwan; Payne, Ursula; Chiu, Basil; Inman, Robert D.

In: Infection and Immunity, Vol. 72, No. 12, 12.2004, p. 7183-7189.

Research output: Contribution to journalArticle

Zhang, Sean Xiang ; Aubin, Jane E. ; Kim, Tae Hwan ; Payne, Ursula ; Chiu, Basil ; Inman, Robert D. / Synovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation. In: Infection and Immunity. 2004 ; Vol. 72, No. 12. pp. 7183-7189.
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abstract = "The mechanisms whereby arthritogenic organisms may induce cartilage and bone erosions in infection-triggered arthritis remain unknown. In this study, we asked whether an arthritogenic organism could contribute to osteoclast differentiation and activation through regulation of the receptor activator of NF-{\^e}{\^A} ligand (RANKL) in synovial fibroblasts. Rat synovial fibroblasts were infected in vitro with Salmonella enterica serovar Typhimurium and monitored over time. The expression of RANKL in resting and infected synovial fibroblasts was quantified by reverse transcription-PCR and Western blotting. Osteoclast progenitors, isolated from femurs of 8-week-old rats and cultured in the presence of macrophage colony-stimulating factor, were cocultured with either infected or noninfected synovial fibroblasts for 2 to 4 days. Differentiation and maturation of osteoclasts were determined by morphology and tartrate-resistant acid phosphatase (TRAP) staining and by a bone resorption bioassay. RANKL expression was undetectable in resting synovial fibroblasts but was dose-dependently upregulated in cells after Salmonella infection. Osteoprotegerin was constitutively expressed by synovial fibroblasts and was not upregulated by infection. Further, we observed the formation of multinucleated TRAP-positive cells and formation of bone resorption pits in cocultures of bone marrow-derived osteoclast precursors with synovial fibroblasts infected with Salmonella but not with heat-killed Salmonella or noninfected cells. Arthritogenic bacteria may alter bone structure via synovial fibroblast intermediaries, since infected synovial fibroblasts (i) upregulate RANKL expression and (ii) enhance osteoclast precursor maturation into multinucleated, TRAP-positive, bone-resorbing, osteoclast-like cells. These data provide a link between infection and osteoclastogenesis. A better understanding of infection-mediated osteoclast differentiation and activation may provide new therapeutic strategies for inflammatory joint disease.",
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