Osteocyte Wnt/β-catenin pathway activation upon mechanical loading is altered in ovariectomized mice
Open accessAbstract
Estrogen levels decline in both sexes with age, but more dramatically in females. Activation of the Wnt/β-catenin signaling pathway is central to the regulation of bone mass accrual and maintenance and in response to mechanical loading. Using the ovariectomized mouse model we examined the effect of estrogen loss on the osteocyte's ability to activate the Wnt/β-catenin pathway following mechanical loading. Female TOPGAL mice underwent ovariectomy (OVX) (n = 10) or sham surgery (n = 10) at 16 weeks of age. Four weeks post-surgery, a single loading session (global strain of 2200 με for 100 cycles at 2 Hz) was performed on the right forearm with the left as a non-loaded control. Mice (n = 5) were sacrificed at 1 or 24 hr post-load. Ulnae were stained for β-catenin activation, femurs were used for μCT and 3-pt bending/biomechanical testing, and tibiae were used for histology analysis and to determine osteocyte lacunar size using SEM and high resolution micro-XCT. A 2.2-fold increase in β-catenin signaling activation was observed 24 hr post-load in the Sham group but did not occur in the OVX group. The OVX group versus control had significant losses (p < 0.05) in trabecular BMD (−8%), BV/TV (−35%) and thickness (−23%), along with cortical thickness (−6%) and periosteal perimeter (−4%). The OVX group had significantly higher trabecular bone osteoclast numbers (63%), OCS/BS (77%) and N.OC/BPm (94%) and a significant decrease in osteoblast number (53%), OBS/BS (37%) and N.OB/BPm (40%) compared to the sham group (p < 0.05). Cortical bone lacunar number/lacunar volume and bone biomechanical properties did not change between groups. Given that the ulna is a cortical bone loading model and the lack of changes in osteocyte lacunar number/volume in cortical bone, which would alter strains experienced by osteocytes, these data suggest the absence of estrogen resulted in intrinsic changes in the ability of the osteocyte to respond to mechanical load, rather than changes in the biomechanical and architectural properties of bone.
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In addition to its effects on bone remodeling, estrogen regulates mechanotransduction in osteocytes by affecting FFSS, Wnt/β-catenin expression, and Cx43 expression.
“In addition to its effects on bone remodeling, estrogen regulates mechanotransduction in osteocytes by affecting FFSS,95 Wnt/β-catenin expression,96 and Cx43 expression.97”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [96]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Jackson, E., Lara-Castillo, N., Akhter, M. P., Dallas, M., Scott, J. M., Ganesh, T., & Johnson, M. L.
- Affiliations
- University of Missouri–Kansas City (US)
- Creighton University (US)
- Corresponding author
- Johnson, Mark L.
- Venue
- Bone Reports
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 15
- Pages
- 101129
- ISSN
- 2352-1872 (ISSN-L)
- PMC
- PMC8455641
- OpenAlex
- W3199800479
- Cited by
- 13
- References
- 59
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bone Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (PO1 AG039355)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt/β-catenin signaling, osteocytes, mechanical loading, ovariectomy, estrogen deficiency, bone loss, trabecular bone, cortical bone, osteoclasts, osteoblasts, bone mechanical properties, bone remodeling
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