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FRI0007 Methyl gallate inhibits osteoclast formation and function through suppressing the AKT and BTK-PLCγ2-CA2+ signaling, and prevents LPS-induced bone loss
  1. M-S Lee1,
  2. JM Baek2,
  3. J-Y Kim2,
  4. W-H Yoo3,
  5. S-J Hong4,
  6. C-H Lee1
  1. 1Internal Medicine, Wonkwang University Hospital
  2. 2Anatomy, School of Medicine, Wonkwang University, Iksan
  3. 3Internal Medicine, Chonbuk National University Medical School, Jeonju
  4. 4Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea, Republic Of

Abstract

Background Methyl gallate, a plant-derived phenolic constituent has been known to possess numerous pharmacological features against inflammation, oxidation, and cancer. But so far, there have been no evidences to describe relationship between methyl gallate and bone metabolism.

Objectives In order to propose a promising candidate for osteoporosis, we performed experiments in this study by using methyl gallate.

Methods we performed screening of methyl gallate utilizing TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis through western blotting and quantitative RT-PCR. Also, we assessed the role of methyl gallate on characteristics of mature osteoclasts. we used LPS-induced bone loss mice as a model of osteoporosis and analyzed using micro-CT system and the right femurs were stained with TRAP and H&E.

Results we observed that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was reconfirmed through transduction of CA-Akt retrovirus and evaluation of Ca2+ influx intensity stained with Fluo-3/AM. Indeed, methyl gallate down-regulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that the administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of LPS in vivo through micro-CT and histology.

Conclusions Consequently, the overall data strongly indicated that methyl gallate could be a useful substance for development of plant-based anti-osteoporotic agent.

Disclosure of Interest None declared

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