R. V. R. Mula, R. Shashidharamurthy / Advances in Bioscience and Biotechnology 4 (2013) 937-940 939
ing different concentrations of TNF-α inhibitor adalimu-
mab and activator RANKL. An hTNF-transgenic de-
structive arthritis mouse model was employed for in vivo
studies of inhibition of osteoclast precursors by the ther-
apeutic. The dose dependent differential effect of TNF-α
on osteoclastogenesis though countered with low doses
of immunotherapeutic inhibitor adalimumab even in the
absence of RANKL, the inflammation of synovium was
not affected. These data suggested that TNF-α alone can
activate the osteoclasts. The mRNA levels of proinflam-
matory mediators such as IL-1, matrix metalloproteinase
(MMP) 3, and MMP13 are significantly upregulated in
untreated hTNF-transgenic mice compared to hTNF-
transgenic mice treated with high concentration (10
mg/kg body weight) of adalimumab. Whereas low dose
(0.1 mg/kg) did not have any affect. Osteoclast associ-
ated genes such as NF-ATc1, cathepsin K, c-Fms, and
M-CSF were also upregulated at higher dose but, inter-
estingly not at lower dose. These data suggest that anti-
resorptive activity of TNF-α was not affected at lower
concentration but not synovial inflammation. Taken to-
gether Binder et al. [18] exemplified the need of control-
ling both cartilage destruction as well as inflammation
mediated by TNF-α during the treatment of rheumatoid
arthritis.
4. ACKNOWLEDGEMENTS
This work was supported by American Heart Association award
(11SDG5710004) to R.S. The authors declare no competing financial
interests.
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