Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice
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| Název: | Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice |
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| Autoři: | Ditte Caroline Andersen, Moustapha Kassem, Casper A. Nipper Nielsen, Florence Figeac, Basem M. Abdallah, Søren P. Sheikh, Charlotte Harken Jensen, Nicholas Ditzel, Karsten Skjødt |
| Zdroj: | Figeac, F, Andersen, D C, Nipper Nielsen, C A, Ditzel, N, Sheikh, S P, Skjødt, K, Kassem, M, Jensen, C H & Abdallah, B M 2018, ' Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice ', Bone, vol. 110, pp. 312-320 . https://doi.org/10.1016/j.bone.2018.02.030 |
| Informace o vydavateli: | Elsevier BV, 2018. |
| Rok vydání: | 2018 |
| Témata: | Monoclonal antibody, 0301 basic medicine, Ovariectomy, Osteoclasts, Intercellular Signaling Peptides and Proteins/immunology, Antibodies, Cell Line, Osteoblasts/drug effects, Mice, 03 medical and health sciences, Antibodies, Neutralizing/therapeutic use, Bone Density, Osteogenesis, Osteoporosis/prevention & control, Animals, Humans, Bone Resorption, Pref-1, 0303 health sciences, Bone Resorption/prevention & control, Osteoblasts, Estrogens/deficiency, Dlk1, Osteoblast, Calcium-Binding Proteins, Bone Density/drug effects, Estrogens, X-Ray Microtomography, Flow Cytometry, Antibodies, Neutralizing, Osteogenesis/drug effects, 3. Good health, Neutralizing/therapeutic use, NIH 3T3 Cells, Osteoclast, Intercellular Signaling Peptides and Proteins, Osteoporosis, Osteoclasts/drug effects, Female, Antibodies/therapeutic use |
| Popis: | Soluble delta-like 1 homolog (DLK1) is a circulating protein that belongs to the Notch/Serrate/delta family, which regulates many differentiation processes including osteogenesis and adipogenesis. We have previously demonstrated an inhibitory effect of DLK1 on bone mass via stimulation of bone resorption and inhibition of bone formation. Further, serum DLK1 levels are elevated and positively correlated to bone turnover markers in estrogen (E)-deficient rodents and women. In this report, we examined whether inhibition of serum DLK1 activity using a neutralizing monoclonal antibody protects from E deficiency-associated bone loss in mice. Thus, we generated mouse monoclonal anti-mouse DLK1 antibodies (MAb DLK1) that enabled us to reduce and also quantitate the levels of bioavailable serum DLK1 in vivo. Ovariectomized (ovx) mice were injected intraperitoneally twice weekly with MAb DLK1 over a period of one month. DEXA-, microCT scanning, and bone histomorphometric analyses were performed. Compared to controls, MAb DLK1 treated ovx mice were protected against ovx-induced bone loss, as revealed by significantly increased total bone mass (BMD) due to increased trabecular bone volume fraction (BV/TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2018.02.030 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/29499415 https://pubmed.ncbi.nlm.nih.gov/29499415/ https://www.sciencedirect.com/science/article/abs/pii/S8756328218300899 https://portal.findresearcher.sdu.dk/da/publications/antibody-based-inhibition-of-circulating-dlk1-protects-from-estro https://findresearcher.sdu.dk:8443/ws/files/137909280/Antibody_based_inhibition_of_circulating_DLK1_protects_from_estrogen_deficiency_induced_bone_loss_in_mice.pdf https://www.ncbi.nlm.nih.gov/pubmed/29499415 https://findresearcher.sdu.dk:8443/ws/files/137909280/Antibody_based_inhibition_of_circulating_DLK1_protects_from_estrogen_deficiency_induced_bone_loss_in_mice.pdf |
| Rights: | Elsevier TDM CC BY NC ND |
| Přístupové číslo: | edsair.doi.dedup.....7e3754b76f7cc73551cea316d4fda0e1 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Soluble delta-like 1 homolog (DLK1) is a circulating protein that belongs to the Notch/Serrate/delta family, which regulates many differentiation processes including osteogenesis and adipogenesis. We have previously demonstrated an inhibitory effect of DLK1 on bone mass via stimulation of bone resorption and inhibition of bone formation. Further, serum DLK1 levels are elevated and positively correlated to bone turnover markers in estrogen (E)-deficient rodents and women. In this report, we examined whether inhibition of serum DLK1 activity using a neutralizing monoclonal antibody protects from E deficiency-associated bone loss in mice. Thus, we generated mouse monoclonal anti-mouse DLK1 antibodies (MAb DLK1) that enabled us to reduce and also quantitate the levels of bioavailable serum DLK1 in vivo. Ovariectomized (ovx) mice were injected intraperitoneally twice weekly with MAb DLK1 over a period of one month. DEXA-, microCT scanning, and bone histomorphometric analyses were performed. Compared to controls, MAb DLK1 treated ovx mice were protected against ovx-induced bone loss, as revealed by significantly increased total bone mass (BMD) due to increased trabecular bone volume fraction (BV/TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss. |
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| ISSN: | 87563282 |
| DOI: | 10.1016/j.bone.2018.02.030 |