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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 15, No. 2, 2016, pp. 299-305
Bioline Code: pr16039
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 15, No. 2, 2016, pp. 299-305

 en Targeting Integrin-β1 Impedes Cytokine-Induced Osteoclast Differentiation: A Potential Pharmacological Intervention in Pathological Osteolysis
Lu, Xing; Zhang, Xing-Lin; Chu, Kai; Zhang, Guo-Dong & Zheng, Yan-Ping


Purpose: To examine whether integrin-β1 is essential for osteoclast differentiation and function and if it can be targeted for pharmacological intervention in pathological osteolysis.
Methods: Control and Integrin-β1 knockdown RAW 264.7 cells were treated with receptor activator of nuclear factor kappa-B (RANKL) or TNF-α and evaluated for osteoclast differentiation. Osteoclast differentiation and function were evaluated by marker protein analysis, tartrate-resistant acid phosphatase (TRAP) and resorption assays. Furthermore, downstream molecular signaling analysis was probed using small molecule inhibitors and blocking antibodies, and evaluated by immunoblotting.
Results: Integrin-β1 knockdown cells showed reduced osteoclast differentiation following TNF-α treatment while no change was seen after RANKL treatment (p < 0.05). Immunoblot-based molecular signaling analysis showed involvement of MAPK kinase signaling in mediating TNF-α/integrin-β1- induced osteoclastogenesis. Finally, when MAPK kinase inhibitor (2.5 and 5 μM; p < 0.05) and integrin- β1 blocking antibody (2.5 and 5 μg/mL; p < 0.05) was used to specifically attenuate TNF-α induced osteoclastogenesis, no change was observed in RANKL-induced osteoclast formation.
Conclusion: The data obtained highlight the role of integrin-β1 in TNF-α-induced osteoclastogenesis, but not in RANKL pathway. Given that, inflammatory cytokine secretions such as TNF-α are progressively implicated in pathological osteolysis, targeting this pathway may attenuate osteolysis in pathological bone tissues.

Osteoclast differentiation; Integrin-β1; Receptor activator of nuclear factor kappa-B; TNF-alpha; Mitogen activated protein kinase; Cytokines; Skeletal disease

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