LIGHT/TNFSF14 regulates estrogen deficiency‐induced bone loss

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 th...

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Bibliographic Details
Published in:The Journal of pathology 2020-04, Vol.250 (4), p.440-451
Main Authors: Brunetti, Giacomina, Storlino, Giuseppina, Oranger, Angela, Colaianni, Graziana, Faienza, Maria F, Ingravallo, Giuseppe, Di Comite, Mariasevera, Reseland, Janne E, Celi, Monica, Tarantino, Umberto, Passeri, Giovanni, Ware, Carl F, Grano, Maria, Colucci, Silvia
Format: Article
Language:English
Subjects:
Bone loss
Bone marrow
Bone mass
Cancellous bone
Cytokines
Hormone replacement therapy
immune cells
Light
LIGHT/TNFSF14
Lymphocytes B
Lymphocytes T
Mesenchyme
Monocytes
Osteoblastogenesis
osteoblasts
Osteoclastogenesis
osteoclasts
osteoimmunology
Osteoporosis
Osteoprotegerin
Ovariectomy
Post-menopause
postmenopausal osteoporosis
RANKL/OPG
Stromal cells
TNF
TRANCE protein
Tumor necrosis factor
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Summary: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.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.5385