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中华关节外科杂志(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 49 -54. doi: 10.3877/cma.j.issn.1674-134X.2022.01.008

综述

神经生长因子在骨关节炎关节软骨中的病理生理作用
王孟玲1, 安丙辰1,()   
  1. 1. 200040 上海,复旦大学附属华东医院
  • 收稿日期:2021-06-23 出版日期:2022-02-01
  • 通信作者: 安丙辰
  • 基金资助:
    上海市科学技术委员会项目(16411964000,21Y-11903100,21MC1930200)

Pathophysiological effects of nerve growth factor on osteoarthritic cartilage

Mengling Wang1, Bingchen An1,()   

  1. 1. Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
  • Received:2021-06-23 Published:2022-02-01
  • Corresponding author: Bingchen An
引用本文:

王孟玲, 安丙辰. 神经生长因子在骨关节炎关节软骨中的病理生理作用[J]. 中华关节外科杂志(电子版), 2022, 16(01): 49-54.

Mengling Wang, Bingchen An. Pathophysiological effects of nerve growth factor on osteoarthritic cartilage[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2022, 16(01): 49-54.

神经生长因子(NGF)是最早被发现的神经营养因子,其在疼痛信号传递中发挥着重要作用。针对NGF的临床止痛药物研发中发现,抑制NGF可以有效地缓解骨关节炎患者的疼痛,但部分患者出现了迅速的关节损害,提示阻断NGF可能会导致关节软骨损伤。目前研究发现NGF及其受体在骨关节炎的关节软骨中表达增高,但其对软骨的影响尚未定论,尚需进一步研究。

Nerve growth factor (NGF) is the first discovered neurotrophic factor, which plays an important role in the pain signal transmission of osteoarthritis. In the Clinical studies of analgesic drugs targeting NGF, it has been found that inhibition of NGF can effectively relieve the pain of patients with osteoarthritis, but some patients have developed rapid joint damage, which suggests that blocking NGF signal may lead to cartilage damage. Current studies have found that the expression of NGF and its receptors are increased in osteoarthritic cartilage, but its effects on cartilage have not been concluded and further study is needed.

[1]
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,201838(12): 705-715.
[2]
Iannone F, De Bari C, Dell'accio F, et al. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes[J]. Rheumatology (Oxford), 2002, 41(12): 1413-1418.
[3]
Yu X, Qi Y, Zhao T, et al. NGF increases FGF2 expression and promotes endothelial cell migration and tube formation through PI3K/Akt and ERK/MAPK pathways in human chondrocytes[J]. Osteoarthritis Cartilage, 2019, 27(3): 526-534.
[4]
Jiang Y, Hu C, Yu S, et al. Cartilage stem/progenitor cells are activated in osteoarthritis via interleukin-1β/nerve growth factor signaling[J/OL]. Arthritis Res Ther, 2015, 17(11): 327. DOI: 10.1186/s13075-015-0840-x.
[5]
Walsh D, Mcwilliams DF, Turley MJ, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis[J]. Rheumatology (Oxford), 2010, 49(10): 1852-1861.
[6]
Pecchi E, Priam S, Gosset M, et al. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain[J/OL]. Arthritis Res Ther, 2014, 16(1): R16. DOI: 10.1186/ar4443.
[7]
Shang X, Zhang L, Jin R, et al. Estrogen regulation of the expression of pain factor NGF in rat chondrocytes[J/OL]. J Pain Res, 2021, 14(11): 931-940. DOI: 10.2147/JPR.S297442..
[8]
Halliday D, Zettler C, Rush RA, et al. Elevated nerve growth factor levels in the synovial fluid of patients with inflammatory joint disease[J]. Neurochem Res, 1998, 23(6): 919-922.
[9]
Dicou E, Masson C, Jabbour W, et al. Increased frequency of NGF in sera of rheumatoid arthritis and systemic lupus erythematosus patients[J]. Neuroreport, 1993, 5(3): 321-324.
[10]
Barthel C, Yeremenko N, Jacobs R, et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis[J/OL]. Arthritis Res Ther, 2009, 11(3): R82. DOI: 10.1186/ar2716.
[11]
Raychaudhuri SP, Raychaudhuri SK. The regulatory role of nerve growth factor and its receptor system in fibroblast-like synovial cells[J]. Scand J Rheumatol, 2009, 38(3): 207-215.
[12]
Del Porto F, Aloe L, Laganà B, et al. Nerve growth factor and brain-derived neurotrophic factor levels in patients with rheumatoid arthritis treated with TNF-alpha blockers[J]. Ann N Y Acad Sci, 2006, 1069(3): 438-443.
[13]
Montagnoli C, Tiribuzi R, Crispoltoni L, et al. β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis[J]. Biol Chem, 2017, 398(9): 1045-1054.
[14]
Rihl M, Kruithof E, Barthel C, et al. Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment[J]. Ann Rheum Dis, 2005, 64(11): 1542-1549.
[15]
Stoppiello LA, Mapp PI, Wilson D, et al. Structural associations of symptomatic knee osteoarthritis[J]. Arthritis Rheumatol, 2014, 66(11): 3018-3027.
[16]
Takano S, Uchida K, Miyagi M, et al. Nerve growth factor regulation by TNF-α and IL-1β in synovial macrophages and fibroblasts in osteoarthritic mice[J/OL]. J Immunol Res, 2016(17): 5706359. DOI: 10.1155/2016/5706359.
[17]
Takano S, Uchida K, Inoue G, et al. Nerve growth factor regulation and production by macrophages in osteoarthritic synovium[J]. Clin Exp Immunol, 2017, 190(2): 235-243.
[18]
Manni L, Lundeberg T, Fiorito S, et al. Nerve growth factor release by human synovial fibroblasts prior to and following exposure to tumor necrosis factor-alpha, interleukin-1 beta and cholecystokinin-8: the possible role of NGF in the inflammatory response[J]. Clin Exp Rheumatol, 2003, 21(5): 617-624.
[19]
Takano S, Uchida K, Itakura M, et al. Transforming growth factor-β stimulates nerve growth factor production in osteoarthritic synovium[J/OL]. BMC Musculoskelet Disord, 2019, 20(1): 204. DOI: 10.1186/s12891-019-2595-z.
[20]
Aso K, Shahtaheri SM, Hill R, et al. Associations of symptomatic knee osteoarthritis with histopathologic features in subchondral bone[J]. Arthritis Rheumatol, 2019, 71(6): 916-924.
[21]
Lane NE, Schnitzer TJ, Birbara CA, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee[J]. N Engl J Med, 2010, 363(16): 1521-1531.
[22]
Miller RE, Malfait AM, Block JA. Current status of nerve growth factor antibodies for the treatment of osteoarthritis pain[J]. Clin Exp Rheumatol, 2017, 35 Suppl 107(5): 85-87.
[23]
Schnitzer TJ, Easton R, Pang S, et al. Effect of tanezumab on joint pain, physical function, and patient global assessment of osteoarthritis among patients with osteoarthritis of the hip or knee: a randomized clinical trial[J]. JAMA, 2019, 322(1): 37-48.
[24]
Berenbaum F, Blanco FJ, Guermazi A, et al. Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period[J]. Ann Rheum Dis, 2020, 79(6): 800-810.
[25]
Hochberg MC, Carrino JA, Schnitzer TJ, et al. Long-Term safety and efficacy of subcutaneous tanezumab versus nonsteroidal antiinflammatory drugs for hip or knee osteoarthritis: a randomized trial[J]. Arthritis Rheumatol, 2021, 73(7): 1167-1177.
[26]
Hochberg MC. Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies[J/OL]. Osteoarthritis Cartilage, 2015, 23 Suppl 1(12): S18-S21. DOI: 10.1016/j.joca.2014.10.005.
[27]
Hochberg MC, Tive LA, Abramson SB, et al. When is osteonecrosis not osteonecrosis?:adjudication of reported serious adverse joint events in the tanezumab clinical development program[J]. Arthritis Rheumatol, 2016, 68(2): 382-391.
[28]
Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis[J]. Biochim Biophys Acta Proteins Proteom, 2012, 1824(1, SI): 133-145.
[29]
Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis[J]. Nature, 2005, 434(7033): 644-648.
[30]
Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis[J]. Nat Rev Rheumatol, 2011, 7(1): 33-42.
[31]
Lu Z, Lei D, Jiang T, et al. Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells[J/OL]. Cell Death Dis, 2017, 8(5): e2801. DOI: 10.1038/cddis.2017.208.
[32]
Huang H, Shank G, Ma L, et al. Nerve growth factor induced after temporomandibular joint inflammation decelerates chondrocyte differentiation[J]. Oral Dis, 2013, 19(6): 604-610.
[33]
Wei X, Sun C, Zhou RP, et al. Nerve growth factor promotes ASIC1a expression via the NF-κB pathway and enhances acid-induced chondrocyte apoptosis[J/OL]. Int Immunopharmacol, 2020, 82(3): 106340. DOI: 10.1016/j.intimp.2020.106340.
[34]
Zhao L, Huang J, Fan Y, et al. Exploration of CRISPR/Cas9-based gene editing as therapy for osteoarthritis[J]. Ann Rheum Dis, 2019, 78(5): 676-682.
[35]
Jiang YZ, Tuan RS. Origin and function of cartilage stem/progenitor cells in osteoarthritis[J]. Nat Rev Rheumatol, 2015, 11(4): 206-212.
[36]
Gigante A, Senesi L, Manzotti S, et al. Effect of nerve growth factor on cultured human chondrocytes[J]. J Biol Regul Homeost Agents, 2016, 30(4 Suppl 1): 1-6.
[37]
Pesesse L, Sanchez C, Henrotin Y. Osteochondral plate angiogenesis: a new treatment target in osteoarthritis[J]. Joint Bone Spine, 2011, 78(2): 144-149.
[38]
袁雪凌,汪爱媛,孟昊业,等.兔膝骨关节炎进程中软骨下骨血管生成的实验研究[J/CD].中华关节外科杂志(电子版),20137(6): 810-814.
[39]
Walsh DA, Bonnet CS, Turner EL, et al. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis[J]. Osteoarthritis Cartilage, 2007, 15(7): 743-751.
[40]
Raychaudhuri SK, Raychaudhuri SP, Weltman H, et al. Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells[J]. Arch Dermatol Res, 2001, 293(6): 291-295.
[41]
Cantarella G, Lempereur L, Presta M, et al. Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo[J]. FASEB J, 2002, 16(10): 1307-1309.
[42]
Moser KV, Reindl M, Blasig I, et al. Brain capillary endothelial cells proliferate in response to NGF, express NGF receptors and secrete NGF after inflammation[J]. Brain Res, 2004, 1017(1/2): 53-60.
[43]
Dolle JP, Rezvan A, Allen FD, et al. Nerve growth factor-induced migration of endothelial cells[J]. J Pharmacol Exp Ther, 2005, 315(3): 1220-1227.
[44]
Park MJ, Kwak HJ, Lee HC, et al. Nerve growth factor induces endothelial cell invasion and cord formation by promoting matrix metalloproteinase-2 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway and AP-2 transcription factor[J]. J Biol Chem, 2007, 282(42): 30485-30496.
[45]
Hemingway F, Taylor R, Knowles HJ, et al. RANKL-independent human osteoclast formation with April, BAFF, NGF, IGF I and IGF II[J]. Bone, 2011, 48(4): 938-944.
[46]
Xu L, Nwosu LN, Burston JJ, et al. The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain[J]. Osteoarthritis Cartilage, 2016, 24(9): 1587-1595.
[47]
Suri S, Walsh DA. Osteochondral alterations in osteoarthritis[J]. Bone, 2012, 51(2, SI): 204-211.
[48]
Strassle BW, Mark L, Leventhal L, et al. Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease[J]. Osteoarthritis Cartilage, 2010, 18(10): 1319-1328.
[49]
Aso K, Shahtaheri SM, Hill R, et al. Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats[J]. Osteoarthritis Cartilage, 2020, 28(9): 1245-1254.
[50]
Obeidat AM, Miller RE, Miller RJ, et al. The nociceptive innervation of the normal and osteoarthritic mouse knee[J]. Osteoarthritis Cartilage, 2019, 27(11): 1669-1679.
[51]
Fuerst M, Bertrand J, Lammers L, et al. Calcification of articular cartilage in human osteoarthritis[J]. Arthritis Rheum, 2009, 60(9): 2694-2703.
[52]
Fuerst M, Niggemeyer O, Lammers L, et al. Articular cartilage mineralization in osteoarthritis of the hip[J/OL]. BMC Musculo-skelet Disord, 2009, 10(12): 166. DOI: 10.1186/1471-2474-10-166.
[53]
Rivera KO, Russo F, Boileau RM, et al. Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion[J/OL]. Sci Rep, 2020, 10(1): 22241. DOI: 10.1038/s41598-020-78983-y.
[54]
Jiang Y, Tuan RS. Role of NGF-TrkA signaling in calcification of articular chondrocytes[J]. FASEB J, 2019, 33(9): 10231-10239.
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