<i>Bcl2l1</i> Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis
Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific <i>Bcl2l1</i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17319 |
| Summary: | Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific <i>Bcl2l1</i>-deficient (<i>Bcl2l1</i><sup>fl/flCre</sup>) mice using 2.3-kb <i>Col1a1</i> Cre. Trabecular bone volume and the trabecular number were lower in <i>Bcl2l1</i><sup>fl/flCre</sup> mice of both sexes than in <i>Bcl2l1</i><sup>fl/fl</sup> mice. In bone histomorphometric analysis, osteoclast parameters were increased in <i>Bcl2l1</i><sup>fl/flCre</sup> mice, whereas osteoblast parameters and the bone formation rate were similar to those in <i>Bcl2l1</i><sup>fl/fl</sup> mice. TUNEL-positive osteoblastic cells and serum TRAP5b levels were increased in <i>Bcl2l1</i><sup>fl/flCre</sup> mice. The deletion of <i>Bcl2l1</i> in osteoblasts induced <i>Tnfsf11</i> expression, whereas the overexpression of <i>Bcl-XL</i> had no effect. In a co-culture of <i>Bcl2l1</i>-deficient primary osteoblasts and wild-type bone-marrow-derived monocyte/macrophage lineage cells, the numbers of multinucleated TRAP-positive cells and resorption pits increased. Furthermore, serum deprivation or the deletion of <i>Bcl2l1</i> in primary osteoblasts increased apoptosis and ATP levels in the medium. Therefore, the reduction in trabecular bone in <i>Bcl2l1</i><sup>fl/flCre</sup> mice may be due to enhanced bone resorption through osteoblast apoptosis and the release of ATP from apoptotic osteoblasts, and <i>Bcl2l1</i> may inhibit bone resorption by preventing osteoblast apoptosis. |
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| ISSN: | 1661-6596 1422-0067 |