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Mice Lacking the a2d1 Auxiliary Voltage Sensitive Calcium Channel Subunit Have Impaired Bone Quantity and Decreased Lean Mass Public Deposited

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MLA citation style

Noonan, Megan, et al. Mice Lacking the A2d1 Auxiliary Voltage Sensitive Calcium Channel Subunit Have Impaired Bone Quantity and Decreased Lean Mass. . 1110. https://mushare.marian.edu/concern/generic_works/d186efa4-7f3f-4ab9-b9ef-bf49ea880bda?locale=en

APA citation style

Noonan, Megan, Kelly, Madison, Robling, Alexander, Farach-Carson Mary, Yi, Xin, Sharma, Karan, & Hum, Julia. (1110). Mice Lacking the a2d1 Auxiliary Voltage Sensitive Calcium Channel Subunit Have Impaired Bone Quantity and Decreased Lean Mass. https://mushare.marian.edu/concern/generic_works/d186efa4-7f3f-4ab9-b9ef-bf49ea880bda?locale=en

Chicago citation style

Noonan, Megan, Kelly, Madison, Robling, Alexander, Farach-Carson Mary, Yi, Xin, Sharma, Karan, and Hum, Julia. Mice Lacking the A2d1 Auxiliary Voltage Sensitive Calcium Channel Subunit Have Impaired Bone Quantity and Decreased Lean Mass. 1110. https://mushare.marian.edu/concern/generic_works/d186efa4-7f3f-4ab9-b9ef-bf49ea880bda?locale=en

Note: These citations are programmatically generated and may be incomplete.

Mechanical loading is critical for bone remodeling. Voltage sensitive calcium channels (VSCCs) influence bone development and responses to loading. The α<sub>2</sub>δ<sub>1</sub> VSCC subunit regulates osteocyte mechanosensation. Here we used α<sub>2</sub>δ<sub>1</sub> knockout mice to determine the role of this subunit in bone development. Dual energy x-ray absorptiometry (DEXA) analyses (n=6/genotype) included male and female mice. Cacna2d1 KO mice had reduced body weight, compared to control mice, by an average of 17.85% (p<0.01) over the ages examined (6, 9, 12, 15, and 18 weeks). Absolute lean mass was reduced in KO mice by an average of 20.68% (p<0.0001). When normalized to body weight, lean mass was reduced in Cacna2d1 KO mice by 7.62% (p<0.01). Whole body bone mineral density (BMD) and bone mineral content (BMC) were reduced by 8.95% (p<0.001) and 26.04% (p<0.0001) respectively. BMD and BMC of the femur was reduced in KO mice by an average of 15.01% (p<0.0001) and 28.62% (p<0.0001) respectively. BMD and BMC of L3-L5 vertebrae were reduced by an average of 11.67% and 23.53% respectively (p<0.0001). μCT analysis of the cancellous compartment of distal femoral metaphyses (n=3 per genotype) revealed that KO mice had decreased trabecular BV/TV (40.43%), decreased trabecular connectivity (77.89%), decreased trabecular number (17.17%), and increased trabecular spacing (22.4%) (p<0.05). Total BMC was decreased in Cacna2d1 KO mice by 18.54%, while cortical BMC was reduced by 13.75% (p=0.0525). Here we show that deletion of α<sub>2</sub>δ<sub>1</sub> in C57BL/6 mice decreased whole body BMC and BMD prominently in trabecular bone, while lean mass was also reduced. We have previously shown that the α<sub>2</sub>δ<sub>1</sub> subunit supports osteocyte responses to force in vitro, thus this subunit may regulate load-induced bone formation. Additionally, as the α<sub>2</sub>δ<sub>1</sub> subunit is the receptor for the antiepileptic drug gabapentin, future work seeks to reveal the mechanisms underlying gabapentin-associated bone loss.

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