切换至 "中华医学电子期刊资源库"
高级检索
中华关节外科杂志(电子版)

中华关节外科杂志(电子版) ›› 2024, Vol. 18 ›› Issue (01) : 106 -117. doi: 10.3877/cma.j.issn.1674-134X.2024.01.014

综述

磨损颗粒影响破骨细胞经典信号通路研究进展
谭飞1, 乔永杰2, 张浩强2, 庄凯鹏2, 曾健康3, 李嘉欢3, 李培杰3, 李栋栋2, 王静3, 周胜虎2,†()   
  1. 1. 730030　兰州，甘肃中医药大学；730050　兰州，解放军联勤保障部队第九四〇医院关节外科
    2. 730050　兰州，解放军联勤保障部队第九四〇医院关节外科
    3. 730030　兰州，甘肃中医药大学
  • 收稿日期:2023-03-28 出版日期:2024-02-01
  • 通信作者: 周胜虎
  • 基金资助:
    甘肃省重点研发计划(21YF5FA154); 甘肃省青年科技基金(20JR5RA588); 甘肃省青年科技基金(21JR7RA014); 部队专项培育项目(2021YXKY014); 兰州市科技计划(2023-2-11); 甘肃中医药大学导师专项(2023YXKY015)

Abrasion particles affect classical signaling pathway of osteoclasts

Fei Tan1, Yongjie Qiao2, Haoqiang Zhang2, Kaipeng Zhuang2, Jiankang Zeng3, Jiahuan Li3, Peijie Li3, Dongdong Li2, Jing Wang3, Shenghu Zhou2,†()   

  1. 1. Gansu University of Chinese Medical, Lanzhou 730003, China; No. 940 Hospital of the Joint Logistics Support Force of PLA, Lanzhou 730050, China
    2. No. 940 Hospital of the Joint Logistics Support Force of PLA, Lanzhou 730050, China
    3. Gansu University of Chinese Medical, Lanzhou 730003, China
  • Received:2023-03-28 Published:2024-02-01
  • Corresponding author: Shenghu Zhou
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

谭飞, 乔永杰, 张浩强, 庄凯鹏, 曾健康, 李嘉欢, 李培杰, 李栋栋, 王静, 周胜虎. 磨损颗粒影响破骨细胞经典信号通路研究进展[J]. 中华关节外科杂志(电子版), 2024, 18(01): 106-117.

Fei Tan, Yongjie Qiao, Haoqiang Zhang, Kaipeng Zhuang, Jiankang Zeng, Jiahuan Li, Peijie Li, Dongdong Li, Jing Wang, Shenghu Zhou. Abrasion particles affect classical signaling pathway of osteoclasts[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(01): 106-117.

全关节置换术是终末期骨关节病最成功的治疗方法之一。尽管该方法取得了很好的效果，但是磨损颗粒的产生以及随后的生物反应导致无菌性假体松动，仍然是全关节置换失败的最常见原因。信号通路激活是引起假体松动骨溶解的关键因素之一。因此，抑制磨损颗粒介导破骨细胞生成的信号通路，对于治疗骨质疏松和溶骨性病变，防止骨丢失是非常必要的。在本综述中，介绍了磨损颗粒通过多条经典信号通路影响破骨细胞生成及相关靶点的激活或抑制，局部缺氧通过信号通路启动自噬影响破骨细胞骨吸收，以期延缓或避免无菌性松动引起的关节翻修，减轻病人经济和心理负担。

关键词: 信号传导, 破骨细胞, 假体失效, 骨质溶解

Total joint replacement is one of the most successful treatments for end-stage osteoarthrosis. Although this method has achieved good results, the production of wear particles and the subsequent biological reaction which leads to aseptic prosthetic loosening, is still the most common cause of the failure of the total joint replacement. Signal pathway activation is one of the key factors causing osteolysis in prosthetic loosening. Therefore, inhibition of wear particles mediated signal pathway, osteoclast formation in treating osteoporosis and bony lesions, it is necessary to prevent bone loss. This review introduced the wear particles by several classic signaling pathways that affect osteoclast formation and related targets for activation or inhibition, local hypoxia by signaling pathways start autophagy affect osteoclast bone resorption, in order to delay or avoid the cause of aseptic loosening joints was renovated and patients to reduce the economic and psychological burden.

Key words: Signaling transduction, Osteoclasts, Prosthesis failure, Osteolysis
图1 多条经典信号通路介导破骨细胞分化注：黑色箭头为促进；红色箭头为抑制；①RANK-RANKL-OPG信号通路；②RANKL-MAPK信号通路；③PI3K/AKT通路；④Wnt信号通路；⑤NLRP3-NF-κB信号通路；⑥CXCL12/CXCR4信号通路
Figure 1 Classic signal pathways induced osteoclasts differentiation
图2 自噬参与破骨细胞分化和迁移注：黑色箭头为促进；红色箭头为抑制；Apoptosis-细胞凋亡；Phagophore-吞噬泡；Mitochonaria-线粒体；Autophagosome-自噬泡；Fusion-融合；Lysosome-溶酶体；Autophagolysosome-自噬溶酶体
Figure 2 Autophagy involves in differentiation and immigration of osteoclasts
图3 自噬在破骨细胞中参与骨代谢的作用注：黑色箭头为促进；红色箭头为抑制；Autophagosome-自噬泡；Autolysosome-自噬溶酶体；Sealing zone-封闭区；Lactic acid-乳酸；Citric acid-柠檬酸；ROS-活性氧自由基
Figure 3 Autophagy participates bone metabolism in osteoclasts
[1]
Mehdipour S, Qoreishi M, Keipourfard A. Comparison of clinical, functional, and radiological outcomes of total knee arthroplasty using conventional and patient-specific instrumentation[J]. Arch Bone Jt Surg, 2020, 8(5): 625－632.
[2]
Sloan M, Premkumar A, ShethNP. Projected volume of primary total joint arthroplasty in the U．S., 2014 to 2030[J]. J Bone Joint Surg Am, 2018, 100(17): 1455－1460.
[3]
王坤正，田润，杨佩. 对我国关节置换外科未来发展的几点思考[J]. 中华创伤骨科杂志，2020, 22(7): 553－555.
[4]
van Dam PA, Verhoeven Y, Trinh XB, et al. RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment[J]. Crit Rev Oncol Hematol, 2019, 133: 85－91.
[5]
Pennanen P, Kallionpää RA, Peltonen S, et al. Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player[J]. Mol Biol Rep, 2021, 48(2): 1243－1254.
[6]
Sharma AR, Jagga S, Chakraborty C, et al. Fibroblast-like-synoviocytes mediate secretion of pro-inflammatory cytokines via ERK and JNK MAPKs in Ti-particle-induced osteolysis[J/OL]. Materials, 2020, 13(16): 3628. DOI: 10.3390/ma13163628.
[7]
Jagga S, Sharma AR, Lee YH, et al. Sclerostin-mediated impaired osteogenesis by fibroblast-like synoviocytes in the particle-induced osteolysis model[J/OL]. Front Mol Biosci, 2021, 8: 666295. DOI: 10.3389/fmolb.2021.666295.
[8]
Cao X. RANKL-RANK signaling regulates osteoblast differentiation and bone formation[J/OL]. Bone Res, 2018, 6: 35. DOI: 10.1038/s41413-018-0040-9.
[9]
谢忠建. 从OPG-RANKL-RANK通路到骨质疏松症分子靶向治疗[J]. 中华骨质疏松和骨矿盐疾病杂志，2022, 15(2): 126－134.
[10]
刘鹏，邓亚鹏，曹国定，等. 人工关节置换术后假体无菌性松动的研究进展[J/CD]. 中华关节外科杂志(电子版), 2020, 14(3): 346－351.
[11]
Wang L, Gao Z, Zhang J, et al. Netrin-1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle-induced osteoclastogenesis[J]. Cell Biol Int, 2021, 45(3): 612－622.
[12]
Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis[J]. Nature, 1999, 397(6717): 315－323.
[13]
Bucay N, Sarosi I, Dunstan CR, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification[J]. Genes Dev, 1998, 12(9): 1260－1268.
[14]
Xue JB, Zhan XL, Wang WJ, et al. OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration[J]. Exp Ther Med, 2016, 12(2): 702－710.
[15]
Gau YC, Yeh TJ, Hsu CM, et al. Pathogenesis and treatment of myeloma-related bone disease[J/OL]. Int J Mol Sci, 2022, 23(6): 3112. DOI: 10.3390/ijms23063112.
[16]
Guo YJ, PanWW, LiuSB, et al. ERK/MAPK signalling pathway and tumorigenesis[J]. Exp Ther Med, 2020, 19(3): 1997－2007.
[17]
Koga Y, Tsurumaki H, Aoki-Saito H, et al. Roles of cyclic AMP response element binding activation in the ERK1/2 and p38 MAPK signalling pathway in central nervous system, cardiovascular system, osteoclast differentiation and mucin and cytokine production[J/OL]. Int J Mol Sci, 2019, 20(6): 1346. DOI: 10.3390/ijms20061346.
[18]
Park HB, Baek KH. E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers[J/OL]. Biochim Biophys Acta Rev Cancer, 2022, 1877(3): 188736. DOI: 10.1016/j.bbcan.2022.188736.
[19]
张晓非，吕震，王小泉，等. 人工关节假体周围无菌性松动的发生机制[J]. 天津医药，2020, 48(6): 572－576.
[20]
Wei CM, Su YJ, Qin X, et al. Monocrotaline suppresses RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced bone loss in vivo[J]. Cell Physiol Biochem, 2018, 48(2): 644－656.
[21]
Aashaq S, Batool A, Andrabi KI. TAK1 mediates convergence of cellular signals for death and survival[J]. Apoptosis, 2019, 24(1－2): 3－20.
[22]
Xu YR, Lei CQ. TAK1-TABs complex: acentral signalosome in inflammatory responses[J/OL]. Front Immunol, 2020, 11: 608976. DOI: 10.3389/fimmu.2020.608976.
[23]
Ha°land E, Moen IN, Veidal E, et al. TAK1-inhibitors are cytotoxic for multiple myeloma cells alone and in combination with melphalan[J]. Oncotarget, 2021, 12(21): 2158－2168.
[24]
Ge C, Xiao G, Jiang D, et al. Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development[J]. J Cell Biol, 2007, 176(5): 709－718.
[25]
Nam JS, Sharma AR, Jagga S, et al. Suppression of osteogenic activity by regulation of WNT and BMP signaling during titanium particle induced osteolysis[J]. J Biomed Mater Res A, 2017, 105(3): 912－926.
[27]
Yang S, Liu G. Targeting the ras/raf/MEK/ERK pathway in hepatocellular carcinoma[J]. Oncol Lett, 2017, 13(3): 1041－1047.
[28]
Li C, Wu Z, Yuan G, et al. Vx-11e protects against titanium-particle-induced osteolysis and osteoclastogenesis by supressing ERK activity[J]. Biochem Biophys Res Commun, 2019, 514(4): 1244－1250.
[29]
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation[J]. Nature, 2003, 423(6937): 337－342.
[30]
O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease[J]. Immunity, 2012, 36(4): 542－550.
[31]
Zhou S, Dai Q, Huang X, et al. STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis[J/OL]. Nat Commun, 2021, 12(1): 6891. DOI: 10.1038/s41467-021-27273-w.
[32]
Song F, Wei C, Zhou L, et al. Luteoloside prevents lipopolysaccharide-induced osteolysis and suppresses RANKL-induced osteoclastogenesis through attenuating RANKL signaling cascades[J]. J Cell Physiol, 2018, 233(2): 1723-1735.
[33]
Yu B, Bai J, Shi J, et al. miR-106b inhibition suppresses inflammatory bone destruction of wear debris-induced periprosthetic osteolysis in rats[J]. J Cell Mol Med, 2020, 24(13): 7490－7503.
[34]
Li HW, Zeng HS. Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis[J]. World J Pediatr, 2020, 16(5): 502－513.
[35]
Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression[J]. Cell, 2008, 133(3): 403－414.
[36]
Ghafouri-Fard S, Abak A, Shoorei H, et al. Regulatory role of microRNAs on PTEN signaling[J/OL]. Biomed Pharmacother, 2021, 133: 110986. DOI: 10.1016/j.biopha.2020.110986.
[37]
Li M, Luo R, Yang W, et al. miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway[J]. In Vitro Cell Dev Biol Anim, 2019, 55(5): 376－386.
[38]
Lu K, Chen Q, Li M, et al. Programmed cell death factor 4 (PDCD4), a novel therapy target for metabolic diseases besides cancer[J]. Free Radic Biol Med, 2020, 159: 150－163.
[39]
Dorrello NV, Peschiaroli A, Guardavaccaro D, et al. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth[J]. Science, 2006, 314(5798): 467－471.
[40]
Sugatani T, Vacher J, Hruska KA. A microRNA expression signature of osteoclastogenesis[J]. Blood, 2011, 117(13): 3648－3657.
[41]
Zhang XY, Li HN, Chen F, et al. Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/β-catenin pathways in osteonecrosis of the femoral head[J]. Saudi Pharm J, 2021, 29(12): 1405－1415.
[42]
蒋昇源，李丹，姜建浩，等. 假体无菌性松动过程中Co2＋对成骨前体细胞的生物学反应[J]. 中国组织工程研究，2021, 25(21): 3292－3299.
[43]
Yang C, Liu W, Zhang X, et al. Naringin increases osteoprotegerin expression in fibroblasts from periprosthetic membrane by the Wnt/β-catenin signaling pathway[J/OL]. J Orthop Surg Res, 2020, 15(1): 600. DOI: 10.1186/s13018-020-02145-z.
[44]
Liu M, Li Y, Yang ST. Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells[J]. J Tissue Eng Regen Med, 2017, 11(1): 276－284.
[45]
Lv J, Sun X, Ma J, et al. Involvement of periostin-sclerostin-Wnt/β-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin[J]. Biochem Biophys Res Commun, 2015, 468(4): 587－593.
[46]
王秋霏，顾叶，彭育沁，等. 人工假体磨损颗粒作用下Wnt/β-catenin信号通路对成骨细胞的影响[J]. 中国组织工程研究，2021, 25(24): 3894－3901.
[47]
陈检文，董立明，蒋科，等. 髋臼假体安装位置与无菌性松动的相关分析[J]. 中国矫形外科杂志，2022, 30(1): 28－32.
[48]
Yin J, Yin Z, Lai P, et al. Pyroptosis in periprosthetic osteolysis[J/OL]. Biomolecules, 2022, 12(12): 1733. DOI: 10.3390/biom12121733.
[49]
van Opdenbosch N, Lamkanfi M. Caspases in cell death, inflammation, and disease[J]. Immunity, 2019, 50(6): 1352－1364.
[50]
Bazrafkan M, Nikmehr B, Shahverdi A, et al. Lipid peroxidation and its role in the expression of NLRP1a and NLRP3genes in testicular tissue of male rats: a model of spinal cord injury[J]. Iran BiomedJ, 2018, 22(3): 151－159.
[51]
彭芃，傅媛，邱俊雄，等. RIPK3在磨损颗粒激活巨噬细胞PRRs/NLRP3信号通路引起人工关节无菌性松动中的作用机制[J]. 中国科学：生命科学，2020, 50(10): 1121－1131.
[52]
Ren H, Kong Y, Liu Z, et al. Selective NLRP3 (pyrin domain-containing protein 3) inflammasome inhibitor reduces brain injury after intracerebral hemorrhage[J]. Stroke, 2018, 49(1): 184－192.
[53]
Yang J, Wise L, Fukuchi KI. TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer’s disease[J/OL]. Front Immunol, 2020, 11: 724. DOI: 10.3389/fimmu.2020.00724.
[54]
Boyce BF. Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts[J]. J Bone Miner Res, 2013, 28(4): 711－722.
[55]
Nakashima T, Hayashi M, Takayanagi H. New insights into osteoclastogenic signaling mechanisms[J]. Trends Endocrinol Metab, 2012, 23(11): 582－590.
[56]
Xing L, Carlson L, Story B, et al. Expression of either NF-kappa B p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption[J]. J Bone Miner Res, 2003, 18(2): 260－269.
[57]
Jämsen E, Pajarinen J, Kouri VP, et al. Tumor necrosis factor primes and metal particles activate the NLRP3 inflammasome in human primary macrophages[J]. Acta Biomater, 2020, 108: 347－357.
[58]
Ping Z, Wang Z, Shi J, et al. Inhibitory effects of melatonin on titanium particle-induced inflammatory bone resorption and osteoclastogenesis via suppression of NF-κB signaling[J]. Acta Biomater, 2017, 62: 362－371.
[59]
Gilbert W, Bragg R, Elmansi AM, et al. Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology[J/OL]. Cytokine, 2019, 123: 154783. DOI: 10.1016/j.cyto.2019.154783.
[60]
Drynda A, Singh G, Buchhorn GH, et al. Metallic wear debris may regulate CXCR4 expression in vitro and in vivo[J]. J Biomed Mater Res A, 2015, 103(6): 1940－1948.
[61]
Mizushima N, Levine B. Autophagy in human diseases[J]. N Engl J Med, 2020, 383(16): 1564－1576.
[62]
Margeta M. Autophagy defects in skeletal myopathies[J]. Annu Rev Pathol, 2020, 15: 261－285.
[63]
Hosokawa N, Hara T, Kaizuka T, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy[J]. Mol Biol Cell, 2009, 20(7): 1981－1991.
[64]
Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins[J]. Autophagy, 2010, 6(6): 764－776.
[65]
Lin HY, Ding JL, Peng YJ, et al. Proteomic and phosphoryproteomic investigations reveal that autophagy-related protein 1, a protein kinase for autophagy initiation, synchronously deploys phosphoregulation on the ubiquitin-like conjugation system in the mycopathogen Beauveria bassiana[J/OL]. mSystems, 2022, 7(1): e0146321. DOI: 10.1128/msystems.01463-21.
[66]
Weidberg H, Shpilka T, Shvets E, et al. LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis[J]. Dev Cell, 2011, 20(4): 444－454.
[67]
Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing[J]. EMBO J, 2000, 19(21): 5720－5728.
[68]
Camuzard O, Breuil V, Carle GF, et al. Autophagy involvement in aseptic loosening of arthroplasty components[J]. J Bone Joint Surg Am, 2019, 101(5): 466－472.
[69]
Wang J, Zhang Y, Cao J, et al. The role of autophagy in bone metabolism and clinical significance[J]. Autophagy, 2023, 19(9): 2409－2427.
[70]
Zhang Y, Cui Y, Wang L, et al. Autophagy promotes osteoclast podosome disassembly and cell motility athrough the interaction of kindlin3 with LC3[J/OL]. Cell Signal, 2020, 67: 109505. DOI: 10.1016/j.cellsig.2019.109505.
[71]
Zhang G, Wang Y, Tang G, et al. Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and-independent autophagic responses[J/OL]. BMC Complement Altern Med, 2019, 19(1): 269. DOI: 10.1186/s12906-019-2691-5.
[72]
Roy M, Roux S. Rab GTPases in osteoclastic bone resorption and autophagy[J/OL]. Int J Mol Sci, 2020, 21(20): 7655. DOI: 10.3390/ijms21207655.
[1] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[2] 周月惠, 江梦钰, 薛宇轩, 卫杨文祥, 凡一诺, 万子艺, 刘予豪, 陈镇秋, 周驰. 线粒体动力学相关蛋白影响破骨细胞分化机制探讨[J]. 中华关节外科杂志(电子版), 2024, 18(01): 60-68.
[3] 皮颖, 王高, 张强, 黄志荣. 年轻患者初次髋关节置换术后关节翻修的原因分析[J]. 中华关节外科杂志(电子版), 2023, 17(03): 430-434.
[4] 凡军, 曹丽萍. 异鼠李素激活p38信号促进鼠间充质干细胞成骨分化[J]. 中华关节外科杂志(电子版), 2021, 15(04): 432-437.
[5] 凡军, 曹丽萍. 体外研究橙皮苷抑制钛颗粒介导的破骨细胞分化[J]. 中华关节外科杂志(电子版), 2020, 14(06): 698-702.
[6] 刘鹏, 邓亚鹏, 曹国定, 高余, 封国超, 刘军, 甄平. 人工关节置换术后假体无菌性松动的研究进展[J]. 中华关节外科杂志(电子版), 2020, 14(03): 346-351.
[7] 伏洪玲, 刘瀚旻. 支气管肺发育不良及肺动脉高压有关信号通路研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(05): 497-505.
[8] 蒋敏, 谢艳艳, 姚延娇, 卢丹. Notch信号通路与妊娠相关疾病发生与发展的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(05): 519-526.
[9] 林伟斌, 朱聪, 洪海森, 黄国锋, 高明明, 吴进, 沙漠, 林灿斌, 陈娜娜, 张晓旭, 丁真奇. 体外周期性压应力对兔胫骨骨折愈合过程成骨与破骨细胞增殖分化能力的影响[J]. 中华损伤与修复杂志(电子版), 2021, 16(04): 289-300.
[10] 郑慧敏, 夏贤友, 刘梦, 姚晓雨, 隋磊. 整联蛋白在骨重建中的作用[J]. 中华口腔医学研究杂志(电子版), 2021, 15(02): 124-128.
[11] 骆鋆攀, 卢嘉蕊, 权晶晶. 破骨细胞融合蛋白的研究进展[J]. 中华口腔医学研究杂志(电子版), 2020, 14(04): 207-213.
[12] 单臻, 李雯, 范远键, 林泽飞, 林颖, 王深明. miR-223通过IGF-1R及NFIA调控乳腺癌细胞及破骨细胞功能的研究[J]. 中华普通外科学文献(电子版), 2020, 14(06): 406-410.
[13] 郭嘉瑜, 邱涛, 喻博. 泛素-蛋白酶体系统在肝缺血再灌注损伤中的研究进展[J]. 中华移植杂志(电子版), 2022, 16(01): 49-54.
[14] 王继荣, 暴一众, 唐颖, 吕晓玲, 杨舟鑫. 吴茱萸碱抑制破骨细胞分化延缓骨丢失的研究[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(02): 86-92.
[15] 房修罗, 赵太云, 陆兴俊. 康复新液联合美沙拉嗪对溃疡性结肠炎活动期患者HMGB1、MCP-1、SOCS-3和Beclin1表达的影响[J]. 中华临床医师杂志(电子版), 2022, 16(03): 246-251.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号