Monocrotaline Suppresses RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo
Autor: | Xiong Qin, Fang Ming Song, Shao Hui Zong, Yi Ji Su, Bo Zhou, Jiake Xu, Jinmin Zhao, Qian Liu, Jia Xin Ding, Cheng Ming Wei |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Lipopolysaccharides musculoskeletal diseases Osteolysis Physiology Osteoclasts Bone Marrow Cells Protective Agents p38 Mitogen-Activated Protein Kinases Bone resorption lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences Mice Osteoclast In vivo Osteogenesis MAPK signaling pathways medicine Animals lcsh:QD415-436 Cells Cultured Cathepsin Monocrotaline biology lcsh:QP1-981 Chemistry Macrophages RANK Ligand Skull JNK Mitogen-Activated Protein Kinases Cell Differentiation medicine.disease Resorption Mice Inbred C57BL Disease Models Animal Proton-Translocating ATPases 030104 developmental biology medicine.anatomical_structure RANKL Cancer research biology.protein Bone marrow Proto-Oncogene Proteins c-fos |
Zdroj: | Cellular Physiology and Biochemistry, Vol 48, Iss 2, Pp 644-656 (2018) |
ISSN: | 1421-9778 1015-8987 |
Popis: | Background/Aims: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. Methods: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. Results: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. Conclusion: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function. |
Databáze: | OpenAIRE |
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