ArticlePloS one2013
KMUP-1 suppresses RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss: roles of MAPKs, Akt, NF-κB and calcium/calcineurin/NFATc1 pathways.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Xanthine Derivative KMUP-3 Alleviates Periodontal Bone Resorption by Inhibiting Osteoclastogenesis and Macrophage Pyroptosis.Journal of periodontal research · 2025Article
- Soluble CD93 lectin-like domain sequesters HMGB1 to ameliorate inflammatory diseases.Theranostics · 2023Article
- AS-605240 Blunts Osteoporosis by Inhibition of Bone Resorption.Drug design, development and therapy · 2023Article
- Xanthine Derivative KMUP-1 Attenuates Experimental Periodontitis by Reducing Osteoclast Differentiation and Inflammation.Frontiers in pharmacology · 2022Article
- The role of CaCell proliferation · 2021Review
- In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis.Biomedicines · 2021Article
- The Role of CaInternational journal of molecular sciences · 2020Review
- New 8-Molecules (Basel, Switzerland) · 2020Article
- An osteogenic helioxanthin derivative suppresses the formation of bone-resorbing osteoclasts.Regenerative therapy · 2019Article
- Combined low-dose LiCl and LY294002 for the treatment of osteoporosis in ovariectomized rats.Journal of orthopaedic surgery and research · 2019Article
- Review
- Recombinant MDA-7/IL24 Suppresses Prostate Cancer Bone Metastasis through Downregulation of the Akt/Mcl-1 Pathway.Molecular cancer therapeutics · 2018Article
- The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review).Molecular medicine reports · 2016Review
- Characterization of DC-STAMP+ Cells in Human Bone Marrow.Journal of bone marrow research · 2013Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE) 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.7 cells and bone loss induced by ovariectomy in mice, and the underlying mechanisms. PRINCIPAL
findingsIn vitro, KMUP-1 inhibited RANKL-induced TRAP activity, the formation of multinucleated osteoclasts and resorption-pit formation. It also inhibited key mediators of osteoclastogenesis including IL-1β, IL-6, TNF-α and HMGB1. In addition, KMUP-1 inhibited RANKL-induced activation of signaling molecules (Akt, MAPKs, calcium and NF-κB), mRNA expression of osteoclastogensis-associated genes (TRAP, MMP-9, Fra-1, and cathepsin K) and transcription factors (c-Fos and NFATc1). Furthermore, most inhibitory effects of KMUP-1 on RANKL-mediated signal activations were reversed by a protein kinase A inhibitor (H89) and a protein kinase G inhibitor (KT5823). In vivo, KMUP-1 prevented loss of bone mineral content, preserved serum alkaline phosphate and reduced serum osteocalcin in ovariectomized mice.
conclusionsKMUP-1 inhibits RANKL-induced osteoclastogenesis in vitro and protects against ovariectomy-induced bone loss in vivo. These effects are mediated, at least in part, by cAMP and cGMP pathways. Therefore, KMUP-1 may have a role in pharmacologic therapy of osteoporosis.
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