MPMBP, a novel bisphosphonate with an antioxidant side chain, stimulates bone formation through inhibition of NF-κB nuclear translocation

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  • Suzuki Keiko
    Department of Pharmacology, School of Dentistry, Ohu University
  • Nagaoka Masahiro
    Department of Pharmacology, School of Dentistry, Ohu University
  • Igarashi Kaoru
    Division of Oral Dysfunction Science, Department of Oral Health and Development Science, Graduate School of Dentistry, Tohoku University
  • Shinoda Hisashi
    Center for Environmental Dentistry, Graduate School of Dentistry, Tohoku University

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  • 骨形成促進作用をもつビスホスホネートMPMBPの開発
  • コツ ケイセイ ソクシン サヨウ オ モツ ビスホスホネート MPMBP ノ カイハツ

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Abstract

<p>Bisphosphonates (BPs) are chemically characterized by a P-C-P bond with two lateral side chains on the carbon atom, and have been widely used as anti-resorptive agents in various metabolic bone diseases. 4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a novel non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. Since inflammation is known to be a cause of the pathological bone resorption, we investigated the effects of MPMBP on bone metabolism both in vitro and in vivo. The results showed that: i) MPMBP dose-dependently increased alkaline-phosphatase activity in a culture of osteoblastic MC3T3-E1 cells, ii) MPMBP increased the synthesis of collagen (type-I) in an organ culture of mouse calvaria, iii) local injection of MPMBP to alveolar bone induced prominent increases in both the bone mass and thickness of alveolar bone at the local site of injection in rabbits, iv) MPMBP increased the mRNA expression of alkaline-phosphatase, type-I collagen, osteocalcin, and bone sialoprotein in MC3T3-E1 cells, v) MPMBP inhibited the translocation of NF-κB/p65 to the nuclei in osteoblasts of cultured mouse calvaria. Taken together, these findings suggest that MPMBP is a promising agent to prevent bone loss, or even accelerate new bone formation, through inducing an uncoupling between bone resorption and bone formation, which is preferable to maintain bone mass and quality.</p>

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