LIGHT/TNFSF14 regulates estrogen deficiency‐induced bone loss
| Autor: | Monica Celi, Giuseppina Storlino, Maria Grano, Giovanni Passeri, Angela Oranger, Carl F. Ware, Giacomina Brunetti, Graziana Colaianni, Silvia Colucci, Giuseppe Ingravallo, Maria Felicia Faienza, Janne E. Reseland, Mariasevera Di Comite, Umberto Tarantino |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Tumor Necrosis Factor Ligand Superfamily Member 14 medicine.medical_specialty Stromal cell Osteoimmunology medicine.medical_treatment TNF Bone Marrow Cells Pathology and Forensic Medicine postmenopausal osteoporosis Settore MED/33 Mice 03 medical and health sciences immune cells 0302 clinical medicine bone loss Osteoprotegerin Osteogenesis LIGHT/TNFSF14 Internal medicine Bone cell medicine Animals Humans Bone Resorption RANKL/OPG osteoimmunology B-Lymphocytes biology Chemistry RANK Ligand osteoblasts osteoclasts ovariectomy Cell Differentiation Estrogens Middle Aged 030104 developmental biology Endocrinology Cytokine medicine.anatomical_structure RANKL 030220 oncology & carcinogenesis biology.protein Tumor necrosis factor alpha Bone marrow Stromal Cells |
| Zdroj: | The Journal of Pathology. 250:440-451 |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.5385 |
| Popis: | Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T-cell co-stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL). Predictably, LIGHT-deficient (Tnfsf14-/- ) mice are protected from ovariectomy-dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag -/- Tnfsf14 -/- ) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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