富血小板血浆与脉冲电磁场联合应用治疗骨关节炎:理论与临床研究的进展
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摘要
背景:骨关节炎是影响人类健康最常见的关节疾患之一,最新的诊疗指南写入物理治疗与关节腔内注射,其中脉冲电磁场治疗与富血小板血浆注射治疗极具潜力,但作用机制及其能否联合使用促进骨关节炎患者康复尚不清楚。目的:总结目前脉冲电磁场联合富血小板血浆注射治疗骨关节炎的相关基础研究带来的理论进展,以及临床应用研究现状。方法:以"Wnt,β-catenin,NF-κB,TLRs,PEMFs,PRP,platelet-rich plasma,OA,osteoarthritis"为关键词,检索了2009至2019年EMbase,Medline,CENTRAL以及万方数据库中相关文献。初检得到文章448篇,筛选后对其中49篇文章进行分析。结果与结论:(1)脉冲电磁场增加细胞中Ca2+浓度改变膜电位,可能引起细胞死亡,也可能在骨形成点沉积、加速骨与软骨的形成;脉冲电磁场对髓核细胞分泌白细胞介素1和肿瘤坏死因子α有抑制作用;(2)富血小板血浆中有非活性的多种生长因子存在,可帮助软骨分化,从而达到保护关节的作用,同时降低了体液和细胞免疫反应;富血小板血浆中的炎症调节因子抑制软骨细胞核因子通路激活的炎症反应,从而抑制白细胞介素1介导的无菌性炎症因子的表达和软骨基质的降解;(3)Toll样受体介导骨髓细胞分化能影响骨代谢,激活的Wnt/β-连环蛋白信号通路可减少骨吸收,同时增加骨形成,Wnt/β-连环蛋白信号传导的介质和下游效应子在骨关节炎中增加;(4)上述研究证实,目前研究发现两者联合治疗骨关节炎的可能机制包括:共同抑制白细胞介素1及肿瘤坏死因子α等炎症因子表达,通过Wnt/β-连环蛋白信号通路协同促进血管内皮生长因子分泌、可能共同调控Toll样受体表达,但尚无研究对比富血小板血浆注射治疗与脉冲电磁场在骨关节炎的疗效,未来除对两者作用机制的研究之外,或许可以将两者结合应用于骨关节炎患者。
BACKGROUND: Osteoarthritis is one of the most common joint diseases affecting human health. Pulsed electromagnetic fields and platelet rich plasma therapy have great potential for physical therapy. However, the precise mechanism of action and whether their combination can promote the rehabilitation of osteoarthritis remain poorly understood.OBJECTIVE: To summarize the theoretical progress of the basic research on the treatment of osteoarthritis by pulsed electromagnetic fields and platelet rich plasma therapy, and the current situation of clinical research.METHODS: A computer-based search of EMbase, Med Line, CENTRAL and Wanfang databases were performed for relevant articles published from 2009 to 2019 with the search terms "Wnt, β-catenin, NF-κB, TLRs, PEMFs, PRP, platelet-rich plasma, OA, osteoarthritis".Initially, 448 articles were retrieved, and finally 49 eligible articles were included for final analysis.RESULTS AND CONCLUSION: Pulsed electromagnetic fields increased Ca~(2+) concentration in cells, altered membrane potential, caused apoptosis or deposit, and accelerated the formation of bone and cartilage. Pulsed electromagnetic fields inhibited the secretion of interleukin-1β and tumor necrosis factor-α by nucleus pulposus cells. There were many non-active growth factors in platelet rich plasma which helped cartilage differentiation, protected the joints and reduced the humoral and cellular immune response. The inflammatory regulators in platelet rich plasma inhibited the inflammatory response of chondrocytes by nuclear factor-κB pathway activation, thus inhibiting the expression of aseptic inflammatory factor mediated by interleukin-1 and the degradation of cartilage matrix. Toll-like receptors mediated bone marrow cell differentiation can affect bone metabolism. Activating Wnt/β-catenin pathway reduced bone absorption, increased bone formation, and increased Wnt/β-catenin signaling-conducted medium and down-stream effectors in osteoarthritis. These results suggest that pulsed electromagnetic fields in combination with platelet rich plasma therapy treated osteoarthritis through co-inhibiting the expression of inflammatory factors such as interleukin-1 and tumor necrosis factor-α, promoting the secretion of vascular endothelial growth factors via the Wnt/β-catenin pathway, and co-regulating the expression of Toll-like receptors.However, little is reported on the efficacy of platelet rich plasma therapy versus pulsed electromagnetic fields on osteoarthritis. Future studies will address on the mechanism of the platelet rich plasma therapy versus pulsed electromagnetic fields and application of their combination in the treatment of osteoarthritis.
BACKGROUND: Osteoarthritis is one of the most common joint diseases affecting human health. Pulsed electromagnetic fields and platelet rich plasma therapy have great potential for physical therapy. However, the precise mechanism of action and whether their combination can promote the rehabilitation of osteoarthritis remain poorly understood.OBJECTIVE: To summarize the theoretical progress of the basic research on the treatment of osteoarthritis by pulsed electromagnetic fields and platelet rich plasma therapy, and the current situation of clinical research.METHODS: A computer-based search of EMbase, Med Line, CENTRAL and Wanfang databases were performed for relevant articles published from 2009 to 2019 with the search terms "Wnt, β-catenin, NF-κB, TLRs, PEMFs, PRP, platelet-rich plasma, OA, osteoarthritis".Initially, 448 articles were retrieved, and finally 49 eligible articles were included for final analysis.RESULTS AND CONCLUSION: Pulsed electromagnetic fields increased Ca~(2+) concentration in cells, altered membrane potential, caused apoptosis or deposit, and accelerated the formation of bone and cartilage. Pulsed electromagnetic fields inhibited the secretion of interleukin-1β and tumor necrosis factor-α by nucleus pulposus cells. There were many non-active growth factors in platelet rich plasma which helped cartilage differentiation, protected the joints and reduced the humoral and cellular immune response. The inflammatory regulators in platelet rich plasma inhibited the inflammatory response of chondrocytes by nuclear factor-κB pathway activation, thus inhibiting the expression of aseptic inflammatory factor mediated by interleukin-1 and the degradation of cartilage matrix. Toll-like receptors mediated bone marrow cell differentiation can affect bone metabolism. Activating Wnt/β-catenin pathway reduced bone absorption, increased bone formation, and increased Wnt/β-catenin signaling-conducted medium and down-stream effectors in osteoarthritis. These results suggest that pulsed electromagnetic fields in combination with platelet rich plasma therapy treated osteoarthritis through co-inhibiting the expression of inflammatory factors such as interleukin-1 and tumor necrosis factor-α, promoting the secretion of vascular endothelial growth factors via the Wnt/β-catenin pathway, and co-regulating the expression of Toll-like receptors.However, little is reported on the efficacy of platelet rich plasma therapy versus pulsed electromagnetic fields on osteoarthritis. Future studies will address on the mechanism of the platelet rich plasma therapy versus pulsed electromagnetic fields and application of their combination in the treatment of osteoarthritis.
引文
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[22]Nabi BN,Sedighinejad A,Mardani-Kivi M,et al.Comparing the effectiveness of intra-articular platelet-rich plasma and corticosteroid injection under ultrasound guidance on pain control of knee osteoarthritis.Iranian Red Crescent Med J.2018;20(3):e62157.
[23]Raeissadat SA,Rayegani SM,Hassanabadi H,et al.Knee osteoarthritis injection choices:platelet-rich plasma(PRP)versus hyaluronic acid(A one-year randomized clinical trial).Clin Med Insights Arthritis Musculoskelet Disord.2015;8:1-8.
[24]吕帅洁,厉驹,何斌,等.富血小板血浆关节内注射治疗膝骨关节炎的前瞻性随机对照研究[J].中华创伤杂志,2016,32(7):626-631.
[25]翟文亮,周亮,刘晖,等.富血小板血浆与透明质酸钠治疗膝关节骨关节炎的临床观察[J].中华关节外科杂志,2017,11(1):96-100.
[26]Ahmad HS,Farrag SE,Okasha AE,et al.Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis.Int J Rheum Dis.2018;21(5):960-966.
[27]Lana JFSD,Weglein A,Sampson SE,et al.Randomized controlled trial comparing hyaluronic acid,platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee.Int J Rheum Dis.2016;12(2):69-78.
[28]Di Sante L,Villani C,Santilli V,et al.Intra-articular hyaluronic acid vs platelet-rich plasma in the treatment of hip osteoarthritis.Med Ultrason.2016;18(4):463-468.
[29]Akan O,Sarikaya NO,Kocyigit H.Efficacy of platelet-rich plasma administration in patients with severe knee osteoarthritis:Can platelet-rich plasma administration delay arthroplasty in this patient population?Int J Clin Exp Med.2018;11(9):9473-9483.
[30]Montanez-Heredia E,Irizar S,Huertas PJ,et al.Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritic knee pain:a randomized clinical trial in the context of the spanish national health care system.Int J Mol Sci.2016;17(7):E1064.
[31]Rayegani SM,Raeissadat SA,Taheri MS,et al.Does intra articular platelet rich plasma injection improve function,pain and quality of life in patients with osteoarthritis of the knee?Arandomized clinical trial.Orthopedic Reviews.2014;6(3):112-117.
[32]Lisi C,Perotti C,Scudeller L,et al.Treatment of knee osteoarthritis:platelet-derived growth factors vs.hyaluronic acid.A randomized controlled trial.Clin Rehabil.2018;32(3):330-339.
[33]Hassan AS,El-Shafey AM,Ahmed HS,et al.Effectiveness of the intra-articular injection of platelet rich plasma in the treatment of patients with primary knee osteoarthritis.Egyptian Rheumatologist.2015;37(3):119-124.
[34]Louis ML,Magalon J,Jouve E,et al.Growth factors levels determine efficacy of platelets rich plasma injection in knee osteoarthritis:a randomized double blind noninferiority trial compared with viscosupplementation.Arthroscopy.2018;34(5):1530-1540.
[35]Mariani E,Canella V,Cattini L,et al.Leukocyte-rich Platelet-rich Plasma injections do not up-modulate intraarticular pro-inflammatory cytokines in the osteoarthritic knee.PLo S One.2016;11(6):e0156137.
[36]Simental-Mendia M,Vilchez-Cavazos JF,Pena-Martinez VM,et al.Leukocyte-poor platelet-rich plasma is more effective than the conventional therapy with acetaminophen for the treatment of early knee osteoarthritis.Arch Orthop Trauma Surg.2016;136(12):1723-1732.
[37]Huang G,Hua S,Yang T,et al.Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors.Exp Ther Med.2018;15(3):3096-3102.
[38]Parate D,Franco-Obregón A,Fr?hlich J,et al.Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields.Sci Rep.2017;7(1):9421.
[39]郭燕庆.富血小板血浆(PRP)治疗膝骨关节炎的临床疗效评价[D].济南:山东大学,2017.
[40]Zou J,Chen Y,Qian J,et al.Effect of a low-frequency pulsed electromagnetic field on expression and secretion of IL-1βand TNF-αin nucleus pulposus cells.J Int Med Res.2017;45(2):462-470.
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[2]中华医学会骨科学分会关节外科学组.骨关节炎诊疗指南(2018年版)[J].中华骨科杂志,2018,38(12):705-715.
[3]薛庆云,王坤正,裴福兴,等.中国40岁以上人群原发性骨关节炎患病状况调查[J].中华骨科杂志,2015,35(12):1206-1212.
[4]Allen KD,Golightly YM.State of the evidence.Curr Opin Rheumatol.2015;27(3):276-83.
[5]Turkiewicz A,Gerhardsson de Verdier M,Engstr?m G,et al.Prevalence of knee pain and knee OA in southern Sweden and the proportion that seeks medical care.Rheum.2015;54(5):827-835.
[6]Driban JB,Eaton CB,Amin M,et al.Glucose homeostasis influences the risk of incident knee osteoarthritis:Data from the osteoarthritis initiative.J Orthop Res.2017;35(10):2282-2287.
[7]Chen A,Gupte C,Akhtar K,et al.The global economic cost of osteoarthritis:how the UK compares.Arthritis.2012;2012:698709.
[8]Kotlarz H,Gunnarsson CL,Fang H,et al.Insurer and out-of-pocket costs of osteoarthritis in the US:evidence from national survey data.Arthritis Rheum.2009;6(12):3546-53.doi:10.1002/art.24984.
[9]Rosen AD,Chastney EE.Effect of long term exposure to 0.5T static magnetic fields on growth and size of GH3 cells.Bioelectromagnetics.2009;30(2):114-119.
[10]Sullivan K,Balin AK,Allen RG.Effects of static magnetic fields on the growth of various types of human cells.Bioelectromagnetics.2011;32(2):140-147.
[11]Galli C,Pedrazzi G,Mattioli-Belmonte M,Guizzardi S.The use of pulsed electromagnetic fields to promote bone responses to biomaterials in vitro and in vivo.Int J Biomater.2018;2018:8935750.
[12]Salamanna F,Veronesi F,Maglio M,et al.New and emerging strategies in platelet-rich plasma application in musculoskeletal regenerative procedures:general overview on still open questions and outlook.Biomed Res Int.2015;2015:846045.
[13]Brossi PM,Moreira JJ,Machado TS,et al.Platelet-rich plasma in orthopedic therapy:a comparative systematic review of clinical and experimental data in equine and human musculoskeletal lesions.BMC Vet Res.2015;11:98.
[14]火焱,陈德志,王昭玲,等.低频脉冲电磁场治疗骨关节炎的有效性及安全性观察[J].中国医药科学,2013,3(13):9-11.
[15]Bagnato GL,Miceli G,Marino N,et al.Pulsed electromagnetic fields in knee osteoarthritis:A double blind,placebo-controlled,randomized clinical trial.Rheumatology(United Kingdom).2016;55(4):755-762.
[16]Ay S,Evcik D.The effects of pulsed electromagnetic fields in the treatment of knee osteoarthritis:a randomized,placebo-controlled trial.Rheumatol Int.2009;29(6):663-666.
[17]Taniguchi Y,Yoshioka T,Kanamori A,et al.Intra-articular platelet-rich plasma(PRP)injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population:a phase I and IIa clinical trial.Nagoya J Med Sci.2018;80(1):39-51.
[18]Smith PA.Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis:an FDA-sanctioned,randomized,double-blind,placebo-controlled clinical trial.Am J Sports Med.2016;44(4):884-891.
[19]Rahimzadeh P,Imani F,Faiz SHR,et al.The effects of injecting intra-articular platelet-rich plasma or prolotherapy on pain score and function in knee osteoarthritis.Clin Interv Aging.2018;13:73-79.
[20]Jubert NJ,Rodriguez L,Reverte-Vinaixa MM,et al.Platelet-rich plasma injections for advanced knee osteoarthritis:a prospective,randomized,double-blinded clinical trial.Orthop J Sports Med.2017;5(2):2325967116689386.
[21]王一帆,李小峰,罗道明,等.不同浓度富血小板血浆治疗膝关节骨性关节炎临床疗效研究[J].陕西医学杂志,2018,47(9):1113-1118.
[22]Nabi BN,Sedighinejad A,Mardani-Kivi M,et al.Comparing the effectiveness of intra-articular platelet-rich plasma and corticosteroid injection under ultrasound guidance on pain control of knee osteoarthritis.Iranian Red Crescent Med J.2018;20(3):e62157.
[23]Raeissadat SA,Rayegani SM,Hassanabadi H,et al.Knee osteoarthritis injection choices:platelet-rich plasma(PRP)versus hyaluronic acid(A one-year randomized clinical trial).Clin Med Insights Arthritis Musculoskelet Disord.2015;8:1-8.
[24]吕帅洁,厉驹,何斌,等.富血小板血浆关节内注射治疗膝骨关节炎的前瞻性随机对照研究[J].中华创伤杂志,2016,32(7):626-631.
[25]翟文亮,周亮,刘晖,等.富血小板血浆与透明质酸钠治疗膝关节骨关节炎的临床观察[J].中华关节外科杂志,2017,11(1):96-100.
[26]Ahmad HS,Farrag SE,Okasha AE,et al.Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis.Int J Rheum Dis.2018;21(5):960-966.
[27]Lana JFSD,Weglein A,Sampson SE,et al.Randomized controlled trial comparing hyaluronic acid,platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee.Int J Rheum Dis.2016;12(2):69-78.
[28]Di Sante L,Villani C,Santilli V,et al.Intra-articular hyaluronic acid vs platelet-rich plasma in the treatment of hip osteoarthritis.Med Ultrason.2016;18(4):463-468.
[29]Akan O,Sarikaya NO,Kocyigit H.Efficacy of platelet-rich plasma administration in patients with severe knee osteoarthritis:Can platelet-rich plasma administration delay arthroplasty in this patient population?Int J Clin Exp Med.2018;11(9):9473-9483.
[30]Montanez-Heredia E,Irizar S,Huertas PJ,et al.Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritic knee pain:a randomized clinical trial in the context of the spanish national health care system.Int J Mol Sci.2016;17(7):E1064.
[31]Rayegani SM,Raeissadat SA,Taheri MS,et al.Does intra articular platelet rich plasma injection improve function,pain and quality of life in patients with osteoarthritis of the knee?Arandomized clinical trial.Orthopedic Reviews.2014;6(3):112-117.
[32]Lisi C,Perotti C,Scudeller L,et al.Treatment of knee osteoarthritis:platelet-derived growth factors vs.hyaluronic acid.A randomized controlled trial.Clin Rehabil.2018;32(3):330-339.
[33]Hassan AS,El-Shafey AM,Ahmed HS,et al.Effectiveness of the intra-articular injection of platelet rich plasma in the treatment of patients with primary knee osteoarthritis.Egyptian Rheumatologist.2015;37(3):119-124.
[34]Louis ML,Magalon J,Jouve E,et al.Growth factors levels determine efficacy of platelets rich plasma injection in knee osteoarthritis:a randomized double blind noninferiority trial compared with viscosupplementation.Arthroscopy.2018;34(5):1530-1540.
[35]Mariani E,Canella V,Cattini L,et al.Leukocyte-rich Platelet-rich Plasma injections do not up-modulate intraarticular pro-inflammatory cytokines in the osteoarthritic knee.PLo S One.2016;11(6):e0156137.
[36]Simental-Mendia M,Vilchez-Cavazos JF,Pena-Martinez VM,et al.Leukocyte-poor platelet-rich plasma is more effective than the conventional therapy with acetaminophen for the treatment of early knee osteoarthritis.Arch Orthop Trauma Surg.2016;136(12):1723-1732.
[37]Huang G,Hua S,Yang T,et al.Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors.Exp Ther Med.2018;15(3):3096-3102.
[38]Parate D,Franco-Obregón A,Fr?hlich J,et al.Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields.Sci Rep.2017;7(1):9421.
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