Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes
| العنوان: | Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes |
|---|---|
| المؤلفون: | Gill Holdsworth, Hollie Allison, Laoise M. McNamara |
| المصدر: | BMC Molecular and Cell Biology, Vol 21, Iss 1, Pp 1-15 (2020) BMC Molecular and Cell Biology |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Osteoclastogenesis, Oscillatory fluid flow, Cathepsin K, Mice, chemistry.chemical_compound, 0302 clinical medicine, Osteogenesis, biology, lcsh:Cytology, Intracellular Signaling Peptides and Proteins, Up-Regulation, Resorption, medicine.anatomical_structure, RANKL, Osteocyte, Female, Signal Transduction, Research Article, musculoskeletal diseases, medicine.medical_specialty, Cell signaling, medicine.drug_class, Sclerostin antibody, 030209 endocrinology & metabolism, Osteocytes, Bone resorption, CCN Intercellular Signaling Proteins, Mechanobiology, 03 medical and health sciences, Osteoclast, Proto-Oncogene Proteins, Internal medicine, medicine, Animals, Bone Resorption, lcsh:QH573-671, Molecular Biology, Adaptor Proteins, Signal Transducing, NFATC Transcription Factors, RANK Ligand, Osteoprotegerin, Membrane Proteins, Estrogen deficiency, Estrogens, Cell Biology, Antibodies, Neutralizing, Chemokine CXCL12, Coculture Techniques, Mice, Inbred C57BL, Wnt Proteins, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Estrogen, Culture Media, Conditioned, biology.protein, Sclerostin |
| الوصف: | Background Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression. Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. Conclusions This study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts. |
| اللغة: | English |
| تدمد: | 2661-8850 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88196f8d32cc423202c9fffd3f78c148 http://link.springer.com/article/10.1186/s12860-020-00322-w |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....88196f8d32cc423202c9fffd3f78c148 |
| قاعدة البيانات: | OpenAIRE |
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