早期兔骨關節炎軟骨CD105+/CD166+細胞及其軟骨分化潛能的實驗研究_《中國修復重建外科雜志》

作者：

王敏 ¹ , Peter Chen ² , 劉超 ¹ , 郝勇 ¹ , 張瑗 ¹ , 張峽 ¹

1 第三軍醫大學新橋醫院骨科（重慶，400037）;;
2 美國加利福利亞大學圣迭哥分校生物工程系及美國圣迭哥 Scripps骨科研究所;

關鍵詞：

軟骨干細胞骨關節炎 CD105 CD166 兔

DOI：

10.7507/1002-1892.20130175

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目的探討早期骨關節炎（osteoarthritis，OA）軟骨組織中CD105+/CD166+細胞的變化規律及其軟骨分化潛能，為軟骨自身修復機制的研究奠定實驗基礎。方法 8～12月齡成年新西蘭大白兔30只，建立右膝OA模型。將實驗分為5組，分別獲取左膝關節正常軟骨細胞（A組），造模后2、4、8周右膝OA軟骨細胞（分別為B、C、D組）以及兔BMSCs（E組）。將各組培養細胞標記CD105和CD166，流式細胞儀分析CD105+/CD166+細胞百分比；并采用免疫磁珠分選法將CD105+/CD166+細胞分選出來。激光共聚焦顯微鏡觀察CD105和CD166在各組細胞中的表達分布情況；成軟骨誘導培養后分別行阿爾新藍細胞化學染色和Ⅱ型膠原免疫組織化學染色；成骨誘導培養后檢測各組鈣含量；成脂誘導培養后行油紅O染色。結果 A、B、C、D組CD105+/CD166+細胞百分比顯著低于E組（P lt; 0.05）；B、C、D組高于A組（P lt; 0.05），D組顯著高于B、C組（P lt; 0.05），但B、C組間差異無統計學意義（P gt; 0.05）。共聚焦顯微鏡觀察示，A、B、C、D組軟骨細胞及E組BMSCs中均可見CD105+、CD166+細胞，各組間無明顯差異。各組細胞微球成軟骨培養1周后，CD105+/CD166+細胞均可見蛋白多糖和Ⅱ型膠原陽性表達，各組間無明顯差異。成骨誘導培養2周時，E組鈣含量顯著高于A、B、C、D組（P lt; 0.05），A、B、C、D組間比較差異無統計學意義（P gt; 0.05）。成脂誘導培養4周，E組可見較多紅色脂滴；A、B、C、D組紅色脂滴數量較E組少，成片狀，大小不一，A、B、C、D組間無差別。結論早期兔OA軟骨組織中CD105+/CD166+細胞增多，這些細胞有軟骨細胞分化潛能。

引用本文： 王敏,Peter Chen,劉超,郝勇,張瑗,張峽. 早期兔骨關節炎軟骨CD105+/CD166+細胞及其軟骨分化潛能的實驗研究. 中國修復重建外科雜志, 2013, 27(7): 793-799. doi: 10.7507/1002-1892.20130175 復制

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12.	Jones BA, Pei M. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration. Tissue Eng Part B Rev, 2012, 18(4): 301-311.
13.	Grogan SP, Miyaki S, Asahara H, et al. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther, 2009, 11(3): R85.
14.	Dowthwaite GP, Bishop JC, Redman SN, et al. The surface of articular cartilage contains a progenitor cell population. J Cell Sci, 2004, 117(Pt 6): 889-897.
15.	Ridley AJ, Schwartz MA, Burridge K, et al. Cell migration: integrating signals from front to back. Science, 2003, 302(5651): 1704-1709.
16.	Kruegel J, Sadowski B, Miosge N. Nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis cartilage. Arthritis Rheum, 2008, 58(5): 1422-1432.
17.	Saito M, Sasho T, Yamaguchi S, et al. Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model. Osteoarthritis Cartilage, 2012, 20(12): 1574-1582.
18.	Heida NM, Muller JP, Cheng IF, et al. Effects of obesity and weight loss on the functional properties of early outgrowth endothelial progenitor cells. J Am Coll Cardiol, 2010, 55(4): 357-367.
19.	Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Artritis Res, 2001, 3(2): 107-113.
20.	Kim HA, Blanco FJ. Cell death and apoptosis in ostearthritic cartilage. Curr Drug Targets, 2007, 8(2): 333-345.
21.	Karlsson C, Stenhamre H, Sandstedt J, et al. Neither Notch1 expression nor cellular size correlate with mesenchymal stem cell properties of adult articular chondrocytes. Cells Tissues Organs, 2008, 187(4): 275-285.
22.	Williams R, Khan IM, Richardson K, et al. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One, 2010, 5(10): e13246.
23.	Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol, 1998, 176(1): 57-66.

1. Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol, 2007, 213(2): 341-347.
2. Fickert S, Fiedler J, Brenner RE. Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining for cell surface markers. Arthritis Res Ther, 2004, 6(5): R422-432.
3. Alsalameh S, Amin R, Gemba T, et al. Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum, 2004, 50(5): 1522-1532.
4. Pretzel D, Linss S, Rochler S, et al. Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage. Arthritis Res Ther, 2011, 13(2): R64.
5. Koelling S, Miosge N. Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther, 2009, 9(11): 1399-1405.
6. Koelling S, Miosge N. Sex differences of chondrogenic progenitor cells in late stages of osteoarthritis. Arthritis Rheum, 2010, 62(4): 1077-1087.
7. Koelling S, Kruegel J, Irmer M, et al. Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis. Cell Stem Cell, 2009, 4(4): 324-335.
8. Pickarski M, Hayami T, Zhuo Y, et al. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord, 2011, 12: 197-212.
9. Johnstone B, Hering TM, Caplan AI, et al. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res, 1998, 238(1): 265-272.
10. Henrotin Y, Pesesse L, Sanchez C. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int, 2012, 23, Suppl 8: S847-851.
11. Bernstein P, Sperling I, Corbeil D, et al. Progenitor cells from cartilageno osteoarthritis-grade-specific differences in stem cell marker expression. Biotechnol Prog, 2013, 29(1): 206-212.
12. Jones BA, Pei M. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration. Tissue Eng Part B Rev, 2012, 18(4): 301-311.
13. Grogan SP, Miyaki S, Asahara H, et al. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther, 2009, 11(3): R85.
14. Dowthwaite GP, Bishop JC, Redman SN, et al. The surface of articular cartilage contains a progenitor cell population. J Cell Sci, 2004, 117(Pt 6): 889-897.
15. Ridley AJ, Schwartz MA, Burridge K, et al. Cell migration: integrating signals from front to back. Science, 2003, 302(5651): 1704-1709.
16. Kruegel J, Sadowski B, Miosge N. Nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis cartilage. Arthritis Rheum, 2008, 58(5): 1422-1432.
17. Saito M, Sasho T, Yamaguchi S, et al. Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model. Osteoarthritis Cartilage, 2012, 20(12): 1574-1582.
18. Heida NM, Muller JP, Cheng IF, et al. Effects of obesity and weight loss on the functional properties of early outgrowth endothelial progenitor cells. J Am Coll Cardiol, 2010, 55(4): 357-367.
19. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Artritis Res, 2001, 3(2): 107-113.
20. Kim HA, Blanco FJ. Cell death and apoptosis in ostearthritic cartilage. Curr Drug Targets, 2007, 8(2): 333-345.
21. Karlsson C, Stenhamre H, Sandstedt J, et al. Neither Notch1 expression nor cellular size correlate with mesenchymal stem cell properties of adult articular chondrocytes. Cells Tissues Organs, 2008, 187(4): 275-285.
22. Williams R, Khan IM, Richardson K, et al. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One, 2010, 5(10): e13246.
23. Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol, 1998, 176(1): 57-66.

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早期兔骨關節炎軟骨CD105+/CD166+細胞及其軟骨分化潛能的實驗研究

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《中國修復重建外科雜志》

早期兔骨關節炎軟骨CD105+/CD166+細胞及其軟骨分化潛能的實驗研究

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