Bone marrow mesenchymal stem cell transplantation increases bone mineral density of an ovariectomized rat model of osteoporosis

doi:10.3969/j.issn.2095-4344.2017.01.009

Abstract

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can be differentiated into osteoblasts, and migrate to lesion sites after transplantation, which have attracted more and more attentions in the research of osteoporosis.
OBJECTIVE: To study the effect of BMSCs transplantation on bone mineral density in an ovariectomized rat model of osteoporosis and its possible mechanism of action.
METHODS: Using the whole bone marrow culture method, BMSCs were isolated from the femur and tibia of juvenile Sprague-Dawley rats. Thirty adult female rats were randomly divided into three groups: control group, ovariectomized group, and cell transplantation group, with 10 rats in each group. Osteoporosis models were made in ovariectomized and cell transplantation group. Then, PBS solution containing 3.5×10⁹/L BMSCs at a dose of 80 μL/kg was injected via the tail vein into the rats in the cell transplantation group, while the same volume of PBS solution was injected in the other two groups. Two weeks later, dual-energy X-ray absorptiometry was used to measure bone mineral density of the femur, lumbar spine and whole body. Serum levels of calcium, phosphorus, alkaline phosphatase and osteocalcin were determined. Micro-CT was used for morphometric analysis of the tibial microstructure.
RESULTS AND CONCLUSION: After ovariectomy, there was a significant reduction in the bone mineral density of the rat femur, lumbar spine and whole body as well as the levels of serum calcium and osteocalcin; however, the phosphorus and alkaline phosphatase levels were increased significantly (P < 0.05 or P < 0.01). These findings indicate the successful preparation of the osteoporosis rat model. Compared with the ovariectomized group, the bone mineral density of the rat femur, lumbar spine or whole body was significantly higher in the cell transplantation group, and significantly increased serum calcium and osteocalcin and significantly decreased phosphorus and alkaline phosphatase levels were also found in the cell transplantation group (P < 0.05). Additionally, the bone volume fraction, number of trabeculae and thickness of trabecular bone were significantly increased in the cell transplantation group compared with the ovariectomized group (P < 0.05). To conclude, our results show that BMSCs can improve the bone mineral density of osteoporosis rats induced by ovariotomy, and thereby promote new bone formation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Osteoporosis, Postmenopausal, Bone Marrow, Mesenchymal Stem Cell Transplantation, Bone Density, Tissue Engineering

CLC Number:

R394.2

Chen Guang-hua, Huang Gui-zhi, Lin Hao, Wu Hao-jun, Chen Hang. Bone marrow mesenchymal stem cell transplantation increases bone mineral density of an ovariectomized rat model of osteoporosis[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(1): 49-53.

Figures/Tables 5

References

[1] 赵文国,张柳,程爱国,等.骨质疏松症诊断的新进展[J].中国综合临床,2002,18(12): 1065-1066.

[2] Padegimas EM, Osei DA. Erratum to: Evaluation and treatment of osteoporotic distal radius fracture in the elderly patient. Curr Rev Musculoskelet Med. 2013;6(2):205.

[3] Riggs BL.Overview of osteoporosis.West J Med. 1991; 154(1):63-77.

[4] 顾本立.骨密度测量[J].世界医疗器械, 1996,3(2):15-18.

[5] 刘忠厚. 骨质疏松学[M].北京:科学出版社, 1998: 397-398.

[6] Eddy DM, Johnston CC, Cummings SR, et al. Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporos Int. 1998;8 Suppl 4:S7-80.

[7] Mazess RB, Peppler WW, Chesnut CH 3rd, et al. Total body bone mineral and lean body mass by dual-photon absorptiometry. II. Comparison with total body calcium by neutron activation analysis. Calcif Tissue Int. 1981;33(4): 361-363.

[8] Pietrobelli A, Formica C, Wang Z, et al. Dual-energy X-ray absorptiometry body composition model: review of physical concepts.Am J Physiol. 1996;271(6 Pt 1):E941-951.

[9] Dinten JM, Robert-coutant C, Darboux M. Dual-energy X-ray absorptiometry using 2D digital radiography detector: Application to bone densitometry. International Society for Optics and Photonics, 2001: 459-468.

[10] 中国健康促进基金会骨质疏松防治中国白皮书编委会.骨质疏松症中国白皮书[J].中华健康管理学杂志, 2009, 3(3):148- 154.

[11] 冉博.大鼠骨髓基质细胞在体外诱导成骨成脂分化的实验研究[D].呼和浩特:内蒙古医学院,2009.

[12] Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A. 1999;96(19):10711-10716.

[13] Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK,et al. Origin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants. Exp Hematol. 1978;6(5):440-444.

[14] Tropel P, Noël D, Platet N, et al. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 2004;295(2):395- 406.

[15] 曹鹏冲. 藏红花提取液对去卵巢大鼠骨质疏松治疗作用的实验研究[D].西安:第四军医大学,2011.

[16] 程晓光,杨定焯,周琦,等.中国女性的年龄相关骨密度、骨丢失率、骨质疏松发生率及参考数据库——多中心合作项目[J].中国骨质疏松杂志,2008,14(4):221-228.

[17] 李险峰.骨质疏松症的分类和分型[J].中国全科医学, 2005,8(16): 1300.

[18] 黄燕兴,胡琪良,安爱华.268 例女性骨质疏松症不同部位骨密度研究[J].中国骨质疏松杂志,2007,13(10): 712-715,708.

[19] 中国老年学学会骨质疏松委员会骨质疏松诊断标准学科组.中国人骨质疏松症建议诊断标准(第二稿) [J].中国骨质疏松杂志, 2000, 6(1):1-3.

[20] Pittenger MF, Mackay AM, Beck SC,et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-147.

[21] Woodbury D, Schwarz EJ, Prockop DJ, et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000;61(4):364-370.

[22] Zhu Y, Liu T, Song K, et al. Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem Funct. 2008;26(6): 664-675.

[23] Kumar S, Wan C, Ramaswamy G, et al. Mesenchymal stem cells expressing osteogenic and angiogenic factors synergistically enhance bone formation in a mouse model of segmental bone defect. Mol Ther. 2010;18(5):1026-1034.

[24] Sun LY, Hsieh DK, Lin PC, et al. Pulsed electromagnetic fields accelerate proliferation and osteogenic gene expression in human bone marrow mesenchymal stem cells during osteogenic differentiation. Bioelectromagnetics. 2010;31(3): 209-219.

[25] Lubis AM, Sandhow L, Lubis VK, et al. Isolation and cultivation of mesenchymal stem cells from iliac crest bone marrow for further cartilage defect management. Acta Med Indones. 2011;43(3):178-184.

[26] Wang CY, Yang HB, Hsu HS, et al. Mesenchymal stem cell-conditioned medium facilitates angiogenesis and fracture healing in diabetic rats. J Tissue Eng Regen Med. 2012;6(7): 559-569.