Tulobuterol Promotes Osteoclast Formation in Co-Culture System

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  • FUKAWA Yukiko
    Department of Periodontology, Showa University School of Dentistry
  • USUI Michihiko
    Department of Periodontology, Showa University School of Dentistry
  • AMANO Hitoshi
    Department of Pharmacology, Showa University School of Dentistry
  • YAMAMOTO Matsuo
    Department of Periodontology, Showa University School of Dentistry
  • YAMADA Shoji
    Department of Pharmacology, Showa University School of Dentistry

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  • Tulobuterolは共存培養系において破骨細胞形成を促進する
  • Tulobuterol ワ キョウソン バイヨウケイ ニ オイテ ハコツ サイボウ ケイセイ オ ソクシン スル

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Abstract

Tulobuterol, which is a representative selective β2-adrenoceptor agonist, is a drug primarily utilized as a therapeutic agent for bronchial asthma consequent to its bronchodilator effect. In recent years, the involvement of β2-adrenoceptor agonist in the bone metabolism regulatory mechanism through the sympathetic nervous system has become clear. With respect to this mechanism, it is believed that bone resorption increases through the β2-adrenoceptor leading to a reduction in bone mass. However, details of this mechanism remain sketchy. Therefore, this investigation sought to clarify the mechanism governing osteoclast formation through the β2-adrenoceptor employing an osteoclastic cell formation system, in which tulobuterol was introduced to the co-culture system of the bone marrow stromal cell line (ST2-T cells) and bone marrow cells. RT-PCR experiment confirmed β2-adrenoceptor expression in the bone marrow stromal cells and osteoblasts. Tulobuterol increased osteoclast number in co-culture system compared with control. In addition, formation of the osteoclast-like cells was inhibited by butoxamine, which is a β2-adrenoceptor antagonist. On the other hand, osteoclasts were not formed despite the introduction of tulobuterol to the single culture system of bone marrow cells. Furthermore, it is believed that the cAMP signal transduction system is involved in the signal transduction of osteoclast-like cell formation given that cyclic adenosine 3′5′-monophosphate (cAMP) levels in ST2-T cells increased in a tulobuterol concentration-dependent manner. Based on these results, it is clear that differentiation from hematopoietic stem cells to osteoclasts occurs through the β2-adrenoceptor, which is expressed in bone marrow stromal cells and osteoblasts.

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