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Updated: May 24, 2026
Murine Orchiectomy and Ovariectomy to Reduce Sex Hormone Production
Published on: November 17, 2023
Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice
Jay J Cao1, Brian R Gregoire, Li Sun
1USDA, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA. Jay.Cao@ars.usda.gov
Abstract:
Proinflammatory cytokines are primary mediators of bone loss in estrogen deficiency. This study determined whether alpha-1 antitrypsin (AAT), a multifunctional protein with proteinase inhibitor and anti-inflammatory activities, mitigates bone loss induced by estrogen deficiency. Mice were either sham-operated or ovariectomized and injected with either AAT or phosphate buffered saline (PBS). Ovariectomy resulted in decreased wet uterus weight, significant bone loss, increased serum leptin concentrations, and higher body weight compared to sham. AAT injection increased tibial trabecular bone volume/total volume and trabecular thickness compared to PBS injection in ovariectomized mice. Ovariectomized mice with AAT treatment had higher uterus weight, lower serum osteocalcin levels, fewer bone marrow tartrate-resistant acid phosphatase-positive osteoclasts, and less expression of calcitonin receptor in bone than that in PBS-injected mice. These data demonstrate that AAT mitigates ovariectomy-induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.
Insights
Alpha-1 antitrypsin (AAT) can reduce bone loss caused by estrogen deficiency. This study found AAT treatment improved bone density and reduced bone resorption markers in mice.
Area of Science:
- Biochemistry
- Immunology
- Orthopedics
Background:
- Estrogen deficiency is a major cause of bone loss.
- Proinflammatory cytokines play a key role in this process.
- Alpha-1 antitrypsin (AAT) possesses anti-inflammatory properties.
Purpose of the Study:
- To investigate the potential of AAT in mitigating bone loss associated with estrogen deficiency.
- To determine the effects of AAT on bone metabolism and resorption markers in an ovariectomized mouse model.
Main Methods:
- Ovariectomy (OVX) was performed on mice to induce estrogen deficiency.
- Mice received either AAT or phosphate-buffered saline (PBS) injections.
- Bone mineral density, bone structure, serum markers, and osteoclast activity were analyzed.
Main Results:
- Ovariectomy led to significant bone loss, increased body weight, and elevated serum leptin.
- AAT treatment in OVX mice increased tibial trabecular bone volume and thickness.
- AAT reduced osteoclast numbers and calcitonin receptor expression, and lowered serum osteocalcin.
Conclusions:
- Alpha-1 antitrypsin (AAT) effectively mitigates ovariectomy-induced bone loss in mice.
- AAT appears to exert its protective effects by inhibiting osteoclast activity and bone resorption.
- These findings suggest AAT as a potential therapeutic agent for postmenopausal osteoporosis.
