Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength
Open accessAbstract
The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild-type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild-type mice. A micro-CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone-formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU-positive osteoblastic cell numbers were increased, TUNEL-positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three-point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild-type mice. The frequency of TUNEL-positive primary osteoblasts was lower in BCLXL transgenic mice than in wild-type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. © 2016 American Society for Bone and Mineral Research.
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The balance between expression of proapoptotic factors Bim and Bak and the prosurvival factor Bcl determines osteoblast life span and, therefore, bone volume and strength.
“The balance between the expression of proapoptotic factors Bim and Bak and the prosurvival factor Bcl determines the osteoblast life span and, therefore, bone volume and strength.284”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [284]
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- Authors
- Moriishi, T., Fukuyama, R., Miyazaki, T., Furuichi, T., Ito, M., & Komori, T.
- Affiliations
- Nagasaki University (JP)
- Hiroshima International University (JP)
- Corresponding author
- Komori, Toshihisa
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-08
- Volume
- 31
- Issue
- 7
- Pages
- 1366-1380
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2261570167
- Cited by
- 33
- References
- 46
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- Bcl-xL, osteoblast apoptosis, osteogenic differentiation, bone volume, trabecular bone, cortical bone, bone strength, osteoporosis, transgenic mice, Col1a1 promoter, osteoblast proliferation, bone mineral density, osteoblast maturation
- MeSH terms
- Cortical Bone, Collagen Type I, alpha 1 Chain, Animals, Gene Expression Regulation, Mice, Transgenic, Osteoblasts, Osteoporosis, Bone Density, Apoptosis, Collagen Type I, bcl-X Protein, Mice, X-Ray Microtomography
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