TRPM8 modulates temperature regulation in a sex-dependent manner without affecting cold-induced bone loss.
TRPM8 modulates temperature regulation in a sex-dependent manner without affecting cold-induced bone loss.
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DOI：
10.1371/journal.pone.0231060
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Motyl KJ
中科院分区：
文献类型：
--
作者：
Lelis Carvalho A;Treyball A;Brooks DJ;Costa S;Neilson RJ;Reagan MR;Bouxsein ML;Motyl KJ
Trpm8（瞬时受体电位阳离子通道，M 亚科，成员 8）由感觉神经元表达，参与环境低温的检测。 TRPM8 活性会触发解偶联蛋白 1 (Ucp1) 依赖性棕色脂肪组织 (BAT) 生热作用的增加。骨密度和骨髓脂肪组织均受到啮齿动物饲养温度和棕色脂肪组织的影响，但尚不清楚 TRPM8 是否参与产热和骨稳态的共同调节。为了解决这个问题，我们检查了 1 岁 Trpm8 敲除小鼠 (Trpm8-KO) 在 4 周的低温挑战后的骨表型。雄性 Trpm8-KO 小鼠的骨密度低于 WT，最引人注目的发现是骨尺寸较小（股骨长度和横截面积），并且与 WT 相比，表现出延迟的冷适应，Dio2 和 Cidea 的 BAT 表达增加。与雄性相比，雌性 Trpm8-KO 小鼠的椎骨微结构参数较低，但体温没有基因型特异性改变。有趣的是，无论男女，寒冷引起的骨小梁丢失都不需要 Trpm8，但 Trpm8 缺失显着抑制了女性的骨髓脂肪组织。总之，我们确定了 TRPM8 在维持体温、骨微结构和骨髓脂肪组织方面的作用存在性别差异。确定低温和最佳可行技术影响骨骼的机制可能有助于改善旨在刺激产热的肥胖治疗的潜在骨骼副作用。
Trpm8 (transient receptor potential cation channel, subfamily M, member 8) is expressed by sensory neurons and is involved in the detection of environmental cold temperatures. TRPM8 activity triggers an increase in uncoupling protein 1 (Ucp1)-dependent brown adipose tissue (BAT) thermogenesis. Bone density and marrow adipose tissue are both influenced by rodent housing temperature and brown adipose tissue, but it is unknown if TRPM8 is involved in the co-regulation of thermogenesis and bone homeostasis. To address this, we examined the bone phenotypes of one-year-old Trpm8 knockout mice (Trpm8-KO) after a 4-week cold temperature challenge. Male Trpm8-KO mice had lower bone mineral density than WT, with smaller bone size (femur length and cross-sectional area) being the most striking finding, and exhibited a delayed cold acclimation with increased BAT expression of Dio2 and Cidea compared to WT. In contrast to males, female Trpm8-KO mice had low vertebral bone microarchitectural parameters, but no genotype-specific alterations in body temperature. Interestingly, Trpm8 was not required for cold-induced trabecular bone loss in either sex, but bone marrow adipose tissue in females was significantly suppressed by Trpm8 deletion. In summary, we identified sex differences in the role of TRPM8 in maintaining body temperature, bone microarchitecture and marrow adipose tissue. Identifying mechanisms through which cold temperature and BAT influence bone could help to ameliorate potential bone side effects of obesity treatments designed to stimulate thermogenesis.
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影响因子：
4.6
作者：
Acharya TK;Kumar S;Tiwari N;Ghosh A;Tiwari A;Pal S;Majhi RK;Kumar A;Das R;Singh A;Maji PK;Chattopadhyay N;Goswami L;Goswami C
通讯作者：
Goswami C
DOI：
10.1007/s00198-016-3634-3
发表时间：
2016-10
期刊：
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
影响因子：
--
作者：
Iwaniec UT;Philbrick KA;Wong CP;Gordon JL;Kahler-Quesada AM;Olson DA;Branscum AJ;Sargent JL;DeMambro VE;Rosen CJ;Turner RT
通讯作者：
Turner RT
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
DOI：
10.1016/j.bbamcr.2017.09.011
发表时间：
2017-12-01
影响因子：
5.1
作者：
Moraes, Maria Nathalia;Monteiro de Assis, Leonardo Vinicius;de Lauro Castrucci, Ana Maria
通讯作者：
de Lauro Castrucci, Ana Maria
影响因子：
5.3
作者：
Reimundez, Alfonso;Fernandez-Pena, Carlos;Senaris, Rosa
通讯作者：
Senaris, Rosa