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Effect of Ermiao Recipe (二妙方) with medicinal guide Angelicae Pubescentis Radix on promoting the homing of bone marrow stem cells to treat cartilage damage in osteoarthritis rats

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Abstract

Objective

To investigate the effect of Ermiao Recipe (二妙方, EMR) with medicinal guide Angelicae Pubescentis Radix (APR) on the homing of bone marrow stem cells (BMSCs) to focal zone in osteoarthritis (OA) rats.

Methods

Forty-eight Sprague-Dawley rats were randomly assigned to the sham-operated, model, EMR, and EMR plus APR groups (12 rats in each group). The OA rat model was induced by anterior cruciate ligament transection and medial meniscus resection. All rats were injected with recombinant human granulocyte colonystimulating factor [rhG-CSF, 30 μg/(kg·d) for continuous 7 days], and rats in the EMR and EMR plus APR groups were treated with EMR or EMR plus APR at 1.6 or 1.9 g/(kg·d) for 3 or 6 weeks, respectively. Cartilage histopathologic changes were observed by hematoxylin and eosin staining. Chondrocytes apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Interleukin-1β (IL-1 β), tumor necrosis factor α (TNF-α), bone morphogenetic protein 2 (BMP-2), and transforming growth factor beta-1 (TGF-β1) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay assay. Matrix metalloproteinase (MMP)-13, tissue inhibitors of metalloproteinase (TIMP)-1, bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemistry assay.

Results

EMR and EMR plus APR significantly inhibited articular cartilage damage and synovium inflammation in OA rats at 3 or 6 weeks of treatment, the most obvious changes in these parameters were found in the EMR plus APR group. At 6 weeks, compared with EMR treatment, EMR plus APR remarkably inhibited chondrocytes apoptosis and the release of IL-1β and TNF-α, obviously decreased MMP-13 expression, and significantly increased expressions of proteoglycan, collagen, type II collagen and TIMP-1, serum levels of BMP-2 and TGF-β1 as well as expressions of BrdU, CD34 and SDF-1 in cartilage articular (P<0.01 or P<0.05).

Conclusion

The medicinal guide APR improved the therapeutic effects of EMR on OA rats by promoting directional homing of BMSCs to focal zone.

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References

  1. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthr Cartil 2009;17:971–979.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Liu W, Wu YH, Liu XY, Xue B, Shen W, Yang K. Metabolic regulatory and anti-oxidative effects of modified Bushen Huoxue Decoction (补肾活血方) on experimental rabbit model of osteoarthritis. Chin J Integr Med 2013;19:459–463.

    Article  CAS  PubMed  Google Scholar 

  3. Gupta PK, Das AK, Chullikana A, Majumdar AS. Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther 2012;3:1–9.

    Article  CAS  Google Scholar 

  4. Koelling S, Miosge N. Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther 2009;9:1399–1405.

    Article  PubMed  Google Scholar 

  5. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331:889–895.

    Article  CAS  PubMed  Google Scholar 

  6. Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000;374:212–234.

    Article  PubMed  Google Scholar 

  7. Luyten FP. Mesenchymal stem cells in osteoarthritis. Curr Opin Rheumatol 2004;16:599–603.

    Article  PubMed  Google Scholar 

  8. Indrawattana N, Chen G, Tadokoro M, Shann LH, Ohgushi H, Tateishi T, et al. Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem Biophys Res Communic 2004;320:914–919.

    Article  CAS  Google Scholar 

  9. Mi Z, Ghivizzani SC, Lechman ER, Jaffurs D, Glorioso JC, Evans CH, et al. Adenovirus-mediated gene transfer of insulin-like growth factor-1 stimulates proteoglycan synthesis in rabbit joints. Arthr Rheum 2000;43:2563–2570.

    Article  CAS  Google Scholar 

  10. Barry FP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res (Part C) 2003;69:250–256.

    Article  CAS  Google Scholar 

  11. Helmuth L. Stem cells hear call of injured tissue. Science 2000;290:1479–1481.

    Article  CAS  PubMed  Google Scholar 

  12. China Pharmacopoeia Committee. Chinese pharmacopoeia. Beijing: Chemical Industry Press; 2010:414.

    Google Scholar 

  13. Liu BY, Huang Y, Liu YL. Modified Ermiao Powder medicine therapy in treating 31 cases of knee osteoarthritis. Hunan J Tradit Chin Med (Chin) 2012;28:53–54.

    CAS  Google Scholar 

  14. Gong GB, Wu HL. The applications of Radix Angelicae Pubescentis in clinic. Modern J Integr Tradit Chin West Med (Chin) 2005;14:2653–2656.

    Google Scholar 

  15. Zhang JL. REN Jian-hua, deputy director of physicians treats rheumatoid arthritis by invigorating Spleen and Kidney. J Gansu Coll Tradit Chin Med (Chin) 2009;26:1–2.

    Google Scholar 

  16. Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 2006;38:234–243.

    Article  PubMed  Google Scholar 

  17. Naito K, Watari T, Muta T, Furuhata A, Iwase H, Igarashi M, et al. Low-intensity pulsed ultrasound (LIPUS) increases the articular cartilage type II collagen in a rat osteoarthritis model. J Orthop Res 2010;28:361–369.

    CAS  PubMed  Google Scholar 

  18. Hayami T, Pickarski M, Wesolowski GA, Mclane J, Bone A, Destefano J, et al. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthr Rheum 2004;50:1193–1206.

    Article  CAS  Google Scholar 

  19. Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. J Bone Joint Surg Am 1971;53:523–537.

    CAS  PubMed  Google Scholar 

  20. Yoshimi T, Kikuchi T, Obara T, Yamaguchi T, Sakakibara Y, Itoh H, et al. Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament. Clin Orthop Relat Res 1994;298:296–304.

    PubMed  Google Scholar 

  21. Kim KM, Kim JM, Yoo YH, Kim JI, Park YC. Cilostazol induces cellular senescence and confers resistance to etoposide-induced apoptosis in articular chondrocytes. Int J Mol Med 2012;29:619.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Bentzon JF, Stenderup K, Hansen FD, Schroder HD, Abdallah BM, Jensen TG, et al. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene. Biochem Biophys Res Commun 2005;330:633–640.

    Article  CAS  PubMed  Google Scholar 

  23. Aigner T, Kim HA. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration. Arthr Rheum 2002;46:1986–1996.

    Article  CAS  Google Scholar 

  24. Eyre D. Collagen of articular cartilage. Arthr Res 2002;4:30–35.

    Article  CAS  Google Scholar 

  25. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumat 2011;7:33–42.

    Article  CAS  Google Scholar 

  26. Aizawa T, Kon T, Einhorn TA, Gerstenfeld LC. Induction of apoptosis in chondrocyte by tumor necrosis factor-alpha. J Orthop Res 2001;19:785–796.

    Article  CAS  PubMed  Google Scholar 

  27. Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2002;39:237–246.

    CAS  PubMed  Google Scholar 

  28. Wetzel M, Li L, Harms KM, Roitbak T, Ventura PB, Rosenberg GA, et al. Tissue inhibitor of metalloproteinases-3 facilitates Fas-mediated neuronal cell death following mild ischemia. Cell Death Differ 2008;15:143–151.

    Article  CAS  PubMed  Google Scholar 

  29. Kong XY, Wang RT, Tian N, Li L, Lin N, Chen WH. Effect of Huogu II Formula (活骨 II 方) with medicinal guide Radix Achyranthis Bidentatae on bone marrow stem cells directional homing to necrosis area after osteonecrosis of the femoral head in rabbit. Chin J Integr Med 2012;18:761–768.

    Article  PubMed  Google Scholar 

  30. Krause DS, Fackler MJ, Civin CI, May WS. CD34: structure, biology, and clinical utility. Blood 1996;87:1–13.

    CAS  PubMed  Google Scholar 

  31. Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001;97:3354–3360.

    Article  CAS  PubMed  Google Scholar 

  32. Lee HH, O’Malley MJ, Friel NA, Chu CR. Effects of doxycycline on mesenchymal stem cell chondrogenesis and cartilage repair. Osteoarthr Cartil 2013;21:385–393.

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to Na Lin  (林 娜).

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Supported by National Natural Science Foundation of China (No. 81072900)

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Xu, Y., Dai, Gj., Liu, Q. et al. Effect of Ermiao Recipe (二妙方) with medicinal guide Angelicae Pubescentis Radix on promoting the homing of bone marrow stem cells to treat cartilage damage in osteoarthritis rats. Chin. J. Integr. Med. 20, 600–609 (2014). https://doi.org/10.1007/s11655-014-1761-2

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  • DOI: https://doi.org/10.1007/s11655-014-1761-2

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