Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.
Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.
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DOI：
10.1210/clinem/dgac117
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发表时间：
2022-05-17
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影响因子：
--
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骨质疏松症是由骨形成和吸收障碍引起的。最近的非人类数据表明，生殖激素Kispeptin在体外直接刺激成骨细胞分化，因此可能具有临床治疗潜力。然而，Kispeptin对人体骨代谢的影响目前尚不清楚。目的：评价Kispeptin在体内外对人骨代谢的影响。体外研究：人成骨细胞和破骨细胞单独培养和联合培养。临床研究：对26名男性进行随机、安慰剂对照、双盲、双向交叉临床研究，调查急性服用Kispeptin(90分钟)对人体骨代谢的影响，每30分钟至+90分钟采一次血。这项体外研究的细胞来自12名男性献血者和8名接受髋关节置换手术的患者。健康男性2 6例，年龄2 6.8 ± 5.8岁。干预措施是服用Kispeptin(与安慰剂相比)。主要观察指标是骨参数和转换标志物的变化。体外培养的人骨髓间充质干细胞与Kisspeptin共同孵育后，碱性磷酸酶水平增加41.1%(P = .0022)，破骨细胞吸收活性抑制高达53.4%(P &t； .0001)，且呈剂量依赖关系。服用Kispeptin的健康男性增加了成骨细胞的活性，总骨钙素最大增加20.3%(P = .021)，羧化骨钙素最大增加24.3%(P = .014)。总而言之，这些数据提供了第一个人类证据，证明Kispeptin促进成骨细胞前体细胞的成骨分化，并在体外抑制骨吸收。此外，Kispeptin可以显著增加健康男性的骨形成标记物骨钙素，但不增加吸收标记物，这与下游的性激素水平无关。因此，Kispeptin在骨质疏松症的治疗中具有临床应用价值。
Osteoporosis results from disturbances in bone formation and resorption. Recent nonhuman data suggest that the reproductive hormone kisspeptin directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. In vitro study: of Mono- and cocultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, 2-way crossover clinical study in 26 men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Cells for the in vitro study were from 12 male blood donors and 8 patients undergoing hip replacement surgery. Twenty-six healthy eugonadal men (age 26.8 ± 5.8 years) were included in the clinical study. The intervention was Kisspeptin (vs placebo) administration. The main outcome measures were changes in bone parameters and turnover markers. Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P = .0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P < .0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P = .021) and 24.3% maximal increase in carboxylated osteocalcin levels (P = .014). Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.
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影响因子：
6.7
作者：
Abbara A;Al-Memar M;Phylactou M;Kyriacou C;Eng PC;Nadir R;Izzi-Engbeaya C;Clarke SA;Mills EG;Daniels E;Huo L;Pacuszka E;Yang L;Patel B;Tan T;Bech P;Comninos AN;Fourie H;Kelsey TW;Bourne T;Dhillo WS
通讯作者：
Dhillo WS
影响因子：
3.7
作者：
Comninos AN;Yang L;O'Callaghan J;Mills EG;Wall MB;Demetriou L;Wing VC;Thurston L;Owen BM;Abbara A;Rabiner EA;Dhillo WS
通讯作者：
Dhillo WS
影响因子：
3.2
作者：
Adekunbi DA;Li XF;Lass G;Shetty K;Adegoke OA;Yeo SH;Colledge WH;Lightman SL;O'Byrne KT
通讯作者：
O'Byrne KT
影响因子：
4
作者：
Cooper, C.;Cole, Z. A.;Holroyd, C. R.;Earl, S. C.;Harvey, N. C.;Dennison, E. M.;Melton, L. J.;Cummings, S. R.;Kanis, J. A.
通讯作者：
Kanis, J. A.
DOI：
10.1016/j.bbrc.2004.11.059
发表时间：
2005-01-21
影响因子：
3.1
作者：
Abdallah, BM;Haack-Sorensen, M;Kassem, M
通讯作者：
Kassem, M