RESEARCH - Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with RA

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Arthritis Res Ther. 2009 Nov 18;11(6):R174.

Connective tissue growth factor promotes articular damage by increased

osteoclastogenesis in patients with rheumatoid arthritis.

Nozawa K, Fujishiro M, Kawasaki M, Kaneko H, Iwabuchi K, Yanagida M,

Suzuki F, Miyazawa K, Takasaki Y, Ogawa H, Takamori K, Sekigawa I.

ABSTRACT:

INTRODUCTION: A protein analysis using a mass spectrometry indicated

that there are serum proteins showing significant quantitative changes

after the administration of infliximab. Among them, connective tissue

growth factor (CTGF) seems to be related to the pathogenesis of

rheumatoid arthritis (RA). Therefore, this study was conducted to

investigate how CTGF is associated with the disease progression of RA.

METHODS: Serum samples were collected from RA patients in active or

inactive disease stages, and before or after treatments with

infliximab. CTGF production was evaluated by ELISA, RT-PCR, indirect

immunofluorescence microscopy, and immunoblotting. Osteoclastogenesis

was evaluated using tartrate-resistant acid phosphatase (TRAP)

staining, a bone resorption assay and osteoclasts specific catalytic

enzymes productions.

RESULTS: The serum concentrations of CTGF in RA were greater than in

normal healthy controls and disease controls. Interestingly, those

were significantly higher in active RA patients compared to inactive

RA patients. Furthermore, the CTGF levels significantly were decreased

by infliximab concomitant with the disease amelioration. In addition,

tumour necrosis factor (TNF)alpha can induce the CTGF production from

synovial fibroblasts even though TNFalpha can oppositely inhibit the

production of CTGF from chondrocytes. CTGF promoted the induction of

the quantitative and qualitative activities of osteoclasts in

combination with M-CSF and receptor activator of NF-kappaB ligand

(RANKL). In addition, we newly found integrin aVb3 on the osteoclasts

as a CTGF receptor.

CONCLUSIONS: These results indicate that aberrant CTGF production

induced by TNFalpha plays a central role for the abnormal osteoclastic

activation in RA patients. Restoration for dysregulation of CTGF

production may contribute to the inhibition of articular destruction

in infliximab treatment.

PMID: 19922639

http://www.ncbi.nlm.nih.gov/pubmed/19922639

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