Effects of intermittent hypoxia on bone growth in rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

WANG Wei ¹ ,  YU Qin ² , LING Jizu ²

1. The First Clinical Medicine College of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
2. The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

YU Qin, Email: yuq701@163.com

Keywords：

Intermittent hypoxia; Rats; Bone; Osteocalcin; Apoptosis

DOI：

10.7507/1671-6205.201805004

Video：

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Objective To study the changes of body weight, body length, tail length, femur length, bone mineral density, serum osteocalcin content and apoptosis of bone cells in rats under intermittent hypoxia condition, so as to explore the effects of intermittent hypoxia on bone growth.Methods Forty healthy male SD rats aged 3 to 4 weeks were selected and divided into 2 groups, 20 rats in each group. Group A: normoxic control group (normal diet and normoxic environment); group B: intermittent hypoxia group (normal feeding and was put into the hypoxic chamber to establish intermittent hypoxia environment), 8 hours a day (09:00 to 17:00), 4 weeks of modeling. The body weight, body length and tail length of the two groups were measured in every morning. At the end of 4 weeks after anesthesia, the body weight, body length, tail length and right femur length were measured. The body weight growth rate, body length growth rate and tail length growth rate were calculated. Blood samples were collected from the abdominal aortic, and the content of serum osteocalcin was measured by enzyme linked immunosorbent assay; the right femur bone mineral density was measured by automatic dual-energy X-ray bone densitometer; the apoptosis of bone cells was detected by immunofluorescence staining+TUNEL.Results The body weight growth rate, body length growth rate, tail length growth rate and right femur length in group A were all higher than those in group B (P<0.05); serum osteocalcin content in group A was higher than that in group B (P<0.05); bone mineral density in group A was higher than that in group B (P<0.05); the apoptotic index of bone cells in group B was higher than that in group A (P<0.05). Pearson correlation analysis showed that the serum osteocalcin content was significantly positively correlated with the growth rate of body length, femoral length and bone mineral density (P< 0.01).Conclusion Intermittent hypoxia could reduce osteocalcin secretion, inhibit bone growth and sclerosis, and induce osteocyte apoptosis, thus delay the bone growth.

Citation： WANG Wei, YU Qin, LING Jizu. Effects of intermittent hypoxia on bone growth in rats. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(3): 271-275. doi: 10.7507/1671-6205.201805004 Copy

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14.	Dewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest, 2015, 147(1): 266-274.
15.	Tomiyama H, Okazaki R, Inoue D, et al. Link between obstructive sleep apnea and increased bone resorption in men. Osteoporos Int, 2008, 19(8): 1185-1192.
16.	Uzkeser H, Yildirim K, Aktan B, et al. Bone mineral density in patients with obstructive sleep apnea syndrome. Sleep Breath, 2013, 17(1): 17-18.
17.	Mariani S, Fiore D, Varone L, et al. Obstructive sleep apnea and bone mineral density in obese patients. Diabetes Metab Syndr Obes, 2012, 5(5): 395-401.
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20.	Peichl P, Griesmacherb A, Marteau R, et al. Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers. Clin Biochem, 2001, 34(2): 131-139.
21.	Ducy P, Desbois C, Boyce B, et al. Increased bone formation in osteocalcin-deficient mice. Nature, 1996, 382(6590): 448.
22.	Brown JP, Delmas PD, Malaval L, et al. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet, 1984, 1(8386): 1091-1093.
23.	Li J, Zhang H, Yang C, et al. An overview of osteocalcin progress. J Bone Mineral Metabolism, 2016, 34(4): 367-379.
24.	Lu W, Kang J. Intermittent hypoxia induced INS-1 cell apoptosis through activation of JNK. Respirology, 2011, 16: 8.
25.	Zhang Z, Hanpeng H. Adiponectin may inhibit chronic intermittent hypoxia-induced endoplasmic reticulum stress and cell apoptosis in genioglossus. Sleep Med, 2013, 14(1): e307.
26.	Li M, Jin T, Miao Y, et al. The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis. Apoptosis, 2015, 20(6): 769-777.

1. Emrick, Bloom B. A Clinical Guide to Pediatric Sleep: Diagnosis and Management of Sleep Problems, Third Edition. J Dev Behav Pediatr, 2016, 37(5): 431.
2. Rosen CL. Clinical features of obstructive sleep apnea hypoventilation syndrome in otherwise healthy children. Pediatr Pulmonol, 2015, 27(6): 403-409.
3. Delrosso LM. Epidemiology and diagnosis of pediatric obstructive sleep apnea. Curr Probl Pediatr Adolesc Health Care, 2016, 46(1): 2-6.
4. Bodenner KA, Jambhekar SK, Com G, et al. Assessment and treatment of obstructive sleep-disordered breathing. Clin Pediatr (Phila), 2014, 53(6): 544.
5. 侯瑾, 康全清, 郑国玺. 儿童阻塞性睡眠呼吸暂停低通气综合征与生长发育迟缓的关系. 中华耳鼻咽喉头颈外科杂志, 2008, 42(3): 174-178.
6. 陈龙, 赵恬, 张佐, 等. 儿童睡眠呼吸障碍研究进展. 世界睡眠医学杂志, 2015, 2(5): 282-286.
7. Li C, Lu J, Zhang B. Development of a novel chronic intermittent hypoxia chamber. Sleep Breath, 2012, 16(1): 177-179.
8. Polšek D, Bago M, Živaljić M, et al. A novel adjustable automated system for inducing chronic intermittent hypoxia in mice. PLoS One, 2017, 12(3): e0174896.
9. 张秀丽, 余勤, 汪小亚, 等. CD73 在慢性间歇性低氧合并高脂饮食条件下大鼠心脏损伤中的作用. 中国呼吸与危重监护杂志, 2017, 16(5): 478-483.
10. Arnett TR, Gibbons DC, Utting JC, et al. Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol, 2010, 196(1): 2-8.
11. 宋子珺, 黄春煌, 任林, 等. 小鼠脂肪干细胞来源外泌体对低氧诱导骨细胞凋亡的影响. 中华口腔医学研究杂志(电子版), 2017, 11(3): 157-163.
12. Miller RG, Segal JB, Ashar BH, et al. High prevalence and correlates of low bone mineral density in young adults with sickle cell disease. Am J Hematol, 2006, 81(4): 236-241.
13. Savaj S, Ghods FJ. Vitamin D, parathyroid hormone, and bone mineral density status in kidney transplant recipients. Iran J Kidney Dis, 2012, 6(4): 295-299.
14. Dewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest, 2015, 147(1): 266-274.
15. Tomiyama H, Okazaki R, Inoue D, et al. Link between obstructive sleep apnea and increased bone resorption in men. Osteoporos Int, 2008, 19(8): 1185-1192.
16. Uzkeser H, Yildirim K, Aktan B, et al. Bone mineral density in patients with obstructive sleep apnea syndrome. Sleep Breath, 2013, 17(1): 17-18.
17. Mariani S, Fiore D, Varone L, et al. Obstructive sleep apnea and bone mineral density in obese patients. Diabetes Metab Syndr Obes, 2012, 5(5): 395-401.
18. Torres M, Montserrat JM, Pavía J, et al. Chronic intermittent hypoxia preserves bone density in a mouse model of sleep apnea. Respir Physiol Neurobiol, 2013, 189(3): 646-648.
19. Sforza E, Thomas T, Barthélémy JC, Collet P, Roche F. Obstructive sleep apnea is associated with preserved bone mineral density in healthy elderly subjects. Sleep, 2013, 36(10): 1509-1515.
20. Peichl P, Griesmacherb A, Marteau R, et al. Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers. Clin Biochem, 2001, 34(2): 131-139.
21. Ducy P, Desbois C, Boyce B, et al. Increased bone formation in osteocalcin-deficient mice. Nature, 1996, 382(6590): 448.
22. Brown JP, Delmas PD, Malaval L, et al. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet, 1984, 1(8386): 1091-1093.
23. Li J, Zhang H, Yang C, et al. An overview of osteocalcin progress. J Bone Mineral Metabolism, 2016, 34(4): 367-379.
24. Lu W, Kang J. Intermittent hypoxia induced INS-1 cell apoptosis through activation of JNK. Respirology, 2011, 16: 8.
25. Zhang Z, Hanpeng H. Adiponectin may inhibit chronic intermittent hypoxia-induced endoplasmic reticulum stress and cell apoptosis in genioglossus. Sleep Med, 2013, 14(1): e307.
26. Li M, Jin T, Miao Y, et al. The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis. Apoptosis, 2015, 20(6): 769-777.

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