Age- and sex-dependent role of osteocytic pannexin1 on bone and muscle mass and strength

被引:19
作者
Aguilar-Perez, Alexandra [1 ]
Pacheco-Costa, Rafael [1 ]
Atkinson, Emily G. [1 ]
Deosthale, Padmini [1 ]
Davis, Hannah M. [1 ]
Essex, Alyson L. [1 ]
Dilley, Julian E. [1 ]
Gomez, Leland [1 ]
Rupert, Joseph E. [4 ]
Zimmers, Teresa A. [1 ,3 ,4 ,5 ]
Thompson, Roger J. [6 ]
Allen, Matthew R. [1 ,2 ]
Plotkin, Lilian I. [1 ,2 ,3 ]
机构
[1] Indiana Univ Sch Med, Dept Anat Cell Biol & Physiol, Indianapolis, IN 46202 USA
[2] Roudebush Vet Adm, Med Ctr, Indianapolis, IN 46202 USA
[3] Indiana Ctr Musculoskeletal Hlth, Indianapolis, IN 46202 USA
[4] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA
[5] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46202 USA
[6] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat, Calgary, AB, Canada
基金
美国国家卫生研究院;
关键词
APOPTOTIC OSTEOCYTES; P2X(7) RECEPTOR; CHANNELS; CONNEXIN-43; RELEASE; MEDIATE; PTH;
D O I
10.1038/s41598-019-50444-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pannexins (Panxs), glycoproteins that oligomerize to form hemichannels on the cell membrane, are topologically similar to connexins, but do not form cell-to-cell gap junction channels. There are 3 members of the family, 1-3, with Panx1 being the most abundant. All Panxs are expressed in bone, but their role in bone cell biology is not completely understood. We now report that osteocytic Panx1 deletion (Panx1(Delta ot)) alters bone mass and strength in female mice. Bone mineral density after reaching skeletal maturity is higher in female Panx1(Delta ot) mice than in control Panx1(fl/fl) mice. Further, osteocytic Panx1 deletion partially prevented aging effects on cortical bone structure and mechanical properties. Young 4-month-old female Panx1(Delta ot) mice exhibited increased lean body mass, even though pannexin levels in skeletal muscle were not affected; whereas no difference in lean body mass was detected in male mice. Furthermore, female Panx1-deficient mice exhibited increased muscle mass without changes in strength, whereas Panx1(Delta ot) males showed unchanged muscle mass and decreased in vivo maximum plantarflexion torque, indicating reduced muscle strength. Our results suggest that osteocytic Panx1 deletion increases bone mass in young and old female mice and muscle mass in young female mice, but has deleterious effects on muscle strength only in males.
引用
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页数:13
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