Masaki Inada

Tokyo University of Agriculture and Technology, Edo, Tōkyō, Japan

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Publications (55)194.71 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation-related parameters and bone resorption-related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation-related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia decreased significantly in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. Copyright © 2015. Published by Elsevier Inc.
    Bone 06/2015; 79. DOI:10.1016/j.bone.2015.06.010 · 3.97 Impact Factor
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    ABSTRACT: Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.
    FEBS Open Bio 06/2015; 390. DOI:10.1016/j.fob.2015.06.003 · 1.52 Impact Factor
  • European Journal of Cancer 11/2014; 50:176. DOI:10.1016/S0959-8049(14)70667-7 · 5.42 Impact Factor
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    ABSTRACT: We examined the effects of heptamethoxyflavone (HMF), a citrus flavonoid on inflammatory bone resorption. HMF suppressed the osteoclast formation and PGE2 production induced by IL-1. In mouse calvarial organ cultures, HMF attenuated the bone resorption elicited by LPS. HMF suppressed bone resorption in the mandibular alveolar bone. HMF may protect against inflammatory bone loss such as periodontal disease.
    Bioscience Biotechnology and Biochemistry 08/2014; 79(1):1-4. DOI:10.1080/09168451.2014.952616 · 1.06 Impact Factor
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    ABSTRACT: S-equol is a natural metabolite of the soy isoflavone, daidzein, produced by intestinal bacteria. S-equol has been shown to have greater estrogenic activity than other soy isoflavones and prevent bone loss in post-menopausal women. Estrogen regulates both bone remodeling and hemopoiesis in the bone marrow, these processes that communicate closely with each other. In this study, we investigated the effect of S-equol on bone mass and gene expression of bone marrow cells in ovariectomized (OVX) mice. Female ddY strain mice, aged 12 weeks, were either sham operated or OVX. The OVX mice were randomly divided into two groups: (1) OVX control and (2) OVX fed a 0.06% (w/w) S-equol supplemented diet. After 2 weeks, the trabecular bone volume of the femoral distal metaphysis was markedly reduced in OVX mice. However, treatment with equol was observed to ameliorate this. Expression of inflammatory-, osteoclastogenesis- and adipogenesis-related genes was increased in OVX mice compared with sham mice, and equol was observed to suppress their expression. The present study demonstrates that equol might ameliorate bone loss caused by estrogen deficiency through regulating hemopoiesis and production of inflammatory cytokines in bone marrow cells.
    Journal of Clinical Biochemistry and Nutrition 07/2013; 53(1):41-8. DOI:10.3164/jcbn.12-123 · 2.19 Impact Factor
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    ABSTRACT: We examined the effects of β-cryptoxanthin, a typical carotenoid, on inflammatory periodontitis. β-Cryptoxanthin suppressed lipopolysaccharide (LPS)-induced osteoclast formation in co-cultures of bone marrow cells and osteoblasts. In a mouse model of periodontitis, it suppressed bone resorption in the mandibular alveolar bone in vitro and restored alveolar bone loss induced by LPS in vivo. β-Cryptoxanthin might protect against periodontal disease.
    Bioscience Biotechnology and Biochemistry 04/2013; 77(4):860-2. DOI:10.1271/bbb.120791 · 1.06 Impact Factor
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    ABSTRACT: We investigated the effects of equol on adipogenesis by measuring lipid accumulation and analyzing the change in adipocyte-related gene expression in MC3T3-L1 cells. Treatment with 10 µM equol tended to increase adipocyte-related gene expression, whereas 100 µM equol reduced lipid accumulation and suppressed the expression of these genes and proteins. Our results suggest that equol regulated adipogenesis in a bi-phasic fashion.
    Bioscience Biotechnology and Biochemistry 01/2013; 77(1). DOI:10.1271/bbb.120677 · 1.06 Impact Factor
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    ABSTRACT: Bombyx mori silk fibroin (SF) shows remarkably earlier calcification than bovine serum albumin, indicating advantage of the SF scaffold for bone regeneration. We provide evidence for the first time, that SF not only activate early differentiation markers of osteoblasts, but also activate expression of the late differentiation markers.
    Journal of Bioscience and Bioengineering 12/2012; 115(5). DOI:10.1016/j.jbiosc.2012.11.021 · 1.88 Impact Factor
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    ABSTRACT: TLR2 forms heterodimers with TLR1 and TLR6, and regulates host defense mechanisms against pathogens. We examined the role of TLR2 heterodimer signaling in osteoclast formation and inflammatory periodontitis. In co-cultures of mouse bone marrow cells and osteoblasts, a TLR2/6 ligand (diacylated lipopeptide designed from Gram-positive bacteria) markedly induced osteoclast formation. A TLR2/1 ligand (triacylated lipopeptide designed from Gram-negative bacteria) also induced osteoclast formation. The osteoclast formation induced by TLR2/6 and TLR2/1 ligands was completely suppressed by indomethacin. Osteoblasts expressed TLR1, 2, 4, and 6 mRNAs, and both TLR2/6 and TLR2/1 ligands induced the expression of COX-2, mPGES-1, and RANKL mRNA, as well as PGE production in osteoblasts. Both TLR2/6 and TLR2/1 ligands induced the resorption of mandibular alveolar bone in organ cultures, and elicited inflammatory periodontitis in vivo. Therefore, TLR2 heterodimer signaling may play a key role in PGE-mediated inflammatory bone loss in periodontal disease.
    Biochemical and Biophysical Research Communications 10/2012; 428(1). DOI:10.1016/j.bbrc.2012.10.016 · 2.30 Impact Factor
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    ABSTRACT: Binding of a series of novel 1α,25-dihydroxyvitamin D(3) (1,25-VD(3)) derivatives, having a nitrogen-linked substituent at the 2α- or 2β-position of the A-ring (2-N-substituted compounds), with the vitamin D receptor (VDR) was investigated by means of computational docking studies. Selected compounds were synthesized by coupling A-ring synthons and/or with CD-ring-bearing bromomethylene under Trost's conditions. The 2α- and 2β-stereoisomers of the A-ring synthons were synthesized from l-serine () as a single chiral source by installing vinyl and propargyl groups at opposite ends of the molecule. The activity of the obtained compounds was evaluated by means of a luciferase-based VDR transcriptional activity assay in NIH3T3 cells. Relatively small substituents incorporating a hydrogen-bonding donor, i.e., NHAc and NHMs, were effective for eliciting VDR transcriptional activity, and 2β-NHMs-1,25-VD(3) () showed the highest activity, being more potent than 1,25-VD(3). Derivatives with bulky substituents were inactive. These new insights into the structure-activity relationships of 1,25-VD(3) derivatives may be helpful in separating the various biological activities of 1,25-VD(3) and in generating novel therapeutic drug candidates.
    Organic & Biomolecular Chemistry 08/2012; 10(38):7826-39. DOI:10.1039/c2ob26017d · 3.56 Impact Factor
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    ABSTRACT: Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/-)) and wild type (WT) mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13(-/-) mice. Granulation tissue in Mmp13(-/-) mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/-) mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/-) mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/-) granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/-) mice compared to WT mice. Mmp13(-/-) mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.
    PLoS ONE 08/2012; 7(8):e42596. DOI:10.1371/journal.pone.0042596 · 3.23 Impact Factor
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    ABSTRACT: Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and maintains bone mass in estrogen-deficient ovariectomized mice. This study examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin suppressed LPS-induced osteoclast formation and bone resorption and suppressed the receptor activator of NFκB ligand-induced osteoclastogenesis in RAW264.7 macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse experimental model for periodontitis by inhibiting LPS-induced bone resorption. PMFs may therefore provide a new therapeutic approach for periodontal bone loss.
    Journal of Pharmacological Sciences 07/2012; 119(4):390-4. DOI:10.1254/jphs.11188SC · 2.36 Impact Factor
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    ABSTRACT: We have invented a mouse model of periodontitis associated with alveolar bone loss induced by lipopolysaccharide. Ovariectomized (OVX) animals are widely used as a model for osteoporosis due to estrogen deficiency. To define the relationship between periodontitis and osteoporosis, we examined the influence of estrogen deficiency on the mouse alveolar bone mass. In OVX mice, bone loss was detected not only in the femur, but also in the alveolar bone, indicating that estrogen deficiency could induce resorption in alveolar bone. In experiments using a combination of osteoporosis and periodontitis models, OVX significantly enhanced the alveolar bone loss in the model of periodontitis. Therefore, postmenopausal osteoporosis may enhance the risk of periodontitis associated with inflammatory alveolar bone resorption.
    Experimental Animals 04/2012; 61(2):183-7. DOI:10.1538/expanim.61.183 · 0.97 Impact Factor
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    ABSTRACT: Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) ligand, regulates nerve-related pain-sensitive signals, inflammation, and cancer growth. Capsaicin suppresses interleukin-1-induced osteoclast differentiation, but its roles in bone tissues and bone diseases are not known. This study examined the effects of capsaicin on inflammatory bone resorption and prostaglandin E (PGE) production induced by lipopolysaccharide (LPS) in vitro and on bone mass in LPS-treated mice in vivo. Capsaicin suppressed osteoclast formation, bone resorption, and PGE production induced by LPS in vitro. Capsaicin suppressed the expression of cyclooxygenase-2 (COX-2) and membrane-bound PGE synthase-1 (mPGES-1) mRNAs and PGE production induced by LPS in osteoblasts. Capsaicin may suppress PGE production by inhibiting the expression of COX-2 and mPGES-1 in osteoblasts and LPS-induced bone resorption by TRPV1 signals because osteoblasts express TRPV1. LPS treatment markedly induced bone loss in the femur in mice, and capsaicin significantly restored the inflammatory bone loss induced by LPS in mice. TRPV1 ligands like capsaicin may therefore be potentially useful as clinical drugs targeting bone diseases associated with inflammatory bone resorption.
    04/2012; 2012:439860. DOI:10.5402/2012/439860
  • Masaki Inada · Chiho Matsumoto · Chisato Miyaura
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    ABSTRACT: Ovariectomized (OVX) animal is a typical experimental model for investigation of postmenopausal osteoporosis due to estrogen deficiency in women. Recently, both OVX mouse and OVX rat are commonly used for the evaluation of bone tissues in the animal model. OVX mouse is appropriate for the study of pathogenesis of postmenopausal osteoporosis, since various gene knockout mice are available for the experiments. OVX rat model is widely used for the evaluation and development of new drug compounds for postmenopausal osteoporosis treatments. On the other hand, orchidectomized (ORX) animal model is excellent in the study of osteoporosis due to androgen deficiency in men. Both OVX and ORX animal exhibits marked bone loss with increased bone resorption. We focused on the feature and evaluation technique for bone tissues in OVX and ORX animals.
    Clinical calcium 02/2011; 21(2):164-70.
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    ABSTRACT: Nobiletin, a polymethoxy flavonoid, prevents cancer and inflammation, but the roles of nobiletin in bone are unclear. We examined the effects of nobiletin on bone resorption in vitro and on bone mass in ovariectomized (OVX) mice in vivo. In vitro, nobiletin suppressed osteoclast formation and bone resorption induced by interleukin (IL)-1. Nobiletin suppressed the expression of cyclooxygenase-2, NFκB-dependent transcription, and prostaglandin E (PGE) production induced by IL-1 in osteoblasts. OVX mice showed severe bone loss in the femur by increased bone resorption due to estrogen deficiency, and nobiletin significantly restored the bone mass. Nobiletin could be beneficial to bone health in postmenopausal women.
    Journal of Pharmacological Sciences 01/2011; 115(1):89-93. DOI:10.1254/jphs.10193SC · 2.36 Impact Factor
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    ABSTRACT: Tissue engineering for skin regeneration is closely related to advances in carrier materials for fibrob-last. To investigate the optimal fibroblast scaffold, we developed a silk protein containing multiple (Ala-Gly-Ala-Gly-Ser-Gly) n sequences, and used it for in vitro evaluations of cell shape, adhesion and matrix production. NIH-3T3 fibroblasts were cultured on silk scaffold and on control culture plates. At 2 hr, fibroblasts cultured on silk scaffold showed round-rose shape, but cells spread on control plates. The numbers of adhesive fibroblasts were the same in both scaffolds, indicating that silk scaffold affects cell shape but not adhesive efficiency. To examine the ef-fects of silk scaffold on cytoskeletal changes of fibrob-lasts, cells were applied to actin staining. Fibroblasts cultured for 2 hr on silk scaffold showed dense actin fibers which formed ring-like structures, while actin stress fibers were formed in cells cultured on control plates. In a long-term culture of 14 days, piled ma-trices produced by fibroblasts have been shown dis-tinctly in cells cultured on silk scaffold compared with cells cultured on control plates. The expression of fi-bronectin mRNA was elevated in fibroblasts cultured on silk scaffold compared with control, but the ex-pression of collagens, type I and type III, mRNAs was similar in fibroblasts cultured on both scaffold. These results indicate that silk scaffold influences cell shape and actin fiber, and enhances matrix production with increased fibronectin. Therefore, silk protein may be an useful scaffold for regenerative therapy in various skin wounds.
    Journal of health science 12/2010; 56(6):738-744. DOI:10.1248/jhs.56.738 · 0.80 Impact Factor
  • Masaki Inada · Chisato Miyaura
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    ABSTRACT: Bone resorption is regulated by various cytokines. In postmenopausal osteoporosis, bone loss due to estrogen deficiency is closely related to the production of bone-resorbing cytokine. Especially, the increased production of IL-1, IL-6 and TNF-α could induce the expression of RANKL in bone tissues to enhance osteoclastogenesis. Relationship between estrogen deficiency and various cytokines is important to clarify the pathogenesis of postmenopausal osteoporosis.
    Clinical calcium 10/2010; 20(10):1467-72.
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    ABSTRACT: Several neurodegenerative diseases involve the selective damage of neuron cells resulting from the accumulation of amyloid fibril formation. Considering that the formation of amyloid fibrils as well as their precursor oligomers is cytotoxic, the agents that prevent the formation of oligomers and/or fibrils might allow the development of a novel therapeutic approach to neurodegenerative diseases. Here, we show pyrroloquinoline quinone (PQQ) inhibits the amyloid fibril formation of the amyloid proteins, amyloid beta (1-42) and mouse prion protein. The fibril formation of mouse prion protein in the presence of PQQ was dramatically prevented. Similarly, the fibril formation of amyloid beta (1-42) also decreased. With further advanced pharmacological approaches, PQQ may become a leading anti-neurodegenerative compound in the treatment of neurodegenerative diseases.
    Prion 01/2010; 4(1):26-31. DOI:10.4161/pri.4.1.10889 · 2.24 Impact Factor
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    ABSTRACT: Naringin is a flavonoid commonly found in citrus fruits. Previous studies have supported a positive as-sociation between fruit consumption and health in-cluding bone quality. To clarify the role of naringin in bone turnover, we examined the effect of naringin on bone mass in mice, and on osteoclast formation in-duced by bone-resorbing cytokine. When mice were orally administered naringin for 2 weeks, femoral bone mineral density (BMD) was clearly elevated compared with control mice. BMD in distal and middle portion was significantly enhanced, but prox-imal BMD was not changed by naringin adminis-tration. In soft-X-ray analysis, a marked accumu-lation of cancellous bone could be detected in distal femoral metasphysis in mice treated with naringin. In cocultures of bone marrow cells and osteoblasts, naringin dose-dependently suppressed the number of osteoclasts formed by treatment with interleukin-1 (IL-1). The size of osteoclasts formed in the presence of naringin was smaller than that induced by IL-1. Naringin enhances bone mass possibly by suppres-sion of osteoclast formation in mice, suggesting the role of the citrus flavonoid on bone health and to pre-vent bone diseases such as osteoporosis.
    Journal of health science 06/2009; 55(3):463-467. DOI:10.1248/jhs.55.463 · 0.80 Impact Factor

Publication Stats

3k Citations
194.71 Total Impact Points


  • 2005–2015
    • Tokyo University of Agriculture and Technology
      • • Division of Biotechnology and Life Science
      • • Graduate School of Engineering
      Edo, Tōkyō, Japan
  • 2004–2008
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2005–2007
    • Massachusetts General Hospital
      • • Department of Medicine
      • • Center for Immunology and Inflammatory Diseases
      Boston, Massachusetts, United States
  • 2001–2003
    • Tokyo University of Pharmacy and Life Science
      • School of Pharmacy
      Tokyo, Tokyo-to, Japan
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1997–1998
    • Showa University
      • Department of Biochemistry
      Shinagawa, Tōkyō, Japan
  • 1996
    • The Nippon Dental University
      • Department of Periodontology
      Edo, Tōkyō, Japan