| Autor: |
Fischer V; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Bülow JM; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Krüger BT; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Ragipoglu D; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Vikman A; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Haffner-Luntzer M; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany., Katsoulis-Dimitriou K; Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.; Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Dudeck A; Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.; Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Ignatius A; Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany. |
| Abstrakt: |
Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss. |
