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Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1 , the gene encoding α2δ1. Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female C57BL/6 mice. Structural differences manifested in both trabecular and cortical bone for males, while the absence of α2δ1 affected only cortical bone in female mice. Deletion of α2δ1 impaired skeletal mechanical properties in both sexes, as measured by three-point bending to failure. While no changes in osteoblast number or activity were found for either sex, male mice displayed a significant increase in osteoclast number, accompanied by increased eroded bone surface and upregulation of genes that regulate osteoclast differentiation. Deletion of α2δ1 also rendered the skeleton insensitive to exogenous mechanical loading in males. While previous work demonstrates that VSCCs are essential for anabolic responses to mechanical loading, the mechanism by which these channels sense and respond to force remained unclear. Our data demonstrate that the α2δ1 auxiliary VSCC subunit functions to maintain baseline bone mass and strength through regulation of osteoclast activity and also provides skeletal mechanotransduction in male mice. These data reveal a molecular player in our understanding of the mechanisms by which VSCCs influence skeletal adaptation. [ABSTRACT FROM AUTHOR]

Recent studies have found a connection between schooling factors and Internet addiction (IA) among adolescents. However, family relationships may be a critical variable for understanding the link between school factors and IA. This study aims to investigate the association between schooling factors of academic performance and school pressure and IA in adolescents while examining the potential mediating role of family relationships in this association. A total of 482 students were recruited through a survey. The survey collected demographic data, the Brief Family Relationship Scale (BFRS), the Internet Addiction Diagnostic Questionnaire (IADQ), and questions that assessed academic performance and school pressure in adolescents. The results revealed that family relationship fully mediated the relationship between school pressure and IA in both early and middle adolescents. In contrast, family relationship fully mediated the relationship between academic performance and IA in early adolescents, only. Our results imply that supportive family relationships help adolescents, especially in the early adolescence stage, manage academic pressure without resorting to maladaptive relationship with the Internet. [ABSTRACT FROM AUTHOR]

Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α 1 ) subunit of VSCCs allows Ca 2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α 2 δ 1 subunit influences gating kinetics of the α 1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α 2 δ 1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1 , the gene encoding α 2 δ 1 . Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α 2 δ 1 diminished bone mineral content and density in both male and female C57BL/6 mice. Structural differences manifested in both trabecular and cortical bone for males, while the absence of α 2 δ 1 affected only cortical bone in female mice. Deletion of α 2 δ 1 impaired skeletal mechanical properties in both sexes, as measured by three-point bending to failure. While no changes in osteoblast number or activity were found for either sex, male mice displayed a significant increase in osteoclast number, accompanied by increased eroded bone surface and upregulation of genes that regulate osteoclast differentiation. Deletion of α 2 δ 1 also rendered the skeleton insensitive to exogenous mechanical loading in males. While previous work demonstrates that VSCCs are essential for anabolic responses to mechanical loading, the mechanism by which these channels sense and respond to force remained unclear. Our data demonstrate that the α 2 δ 1 auxiliary VSCC subunit functions to maintain baseline bone mass and strength through regulation of osteoclast activity and also provides skeletal mechanotransduction in male mice. These data reveal a molecular player in our understanding of the mechanisms by which VSCCs influence skeletal adaptation., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)