成纤维细胞生长因子在骨关节炎的研究进展
Research Progress of Fibroblast Growth Factor Signalling in Osteoarthritis
DOI: 10.12677/ACM.2023.132359, PDF,   
作者: 何子轩:浙江大学医学院,浙江 杭州 ;陈海啸*:浙江大学附属台州医院,浙江 临海
关键词: 成纤维细胞生长因子骨关节炎软骨退化Fibroblast Growth Factor Osteoarthritis Cartilage Degeneration
摘要: 骨关节炎是一种退行性慢性关节疾病,目前临床治疗效果不佳,严重影响病人的生活质量。成纤维细胞生长因子信号通路不仅参与调节正常的生理过程,在骨关节炎的发生发展中也扮演关键角色,尤其是在软骨代谢及合成方面意义重大。本文就近年来FGF/FGFR信号通路参与骨关节炎发生发展、软骨及软骨下骨退变机制以及与该通路相关的靶点在骨关节炎治疗中的研究现状进行综述。
Abstract: Osteoarthritis (OA) is a degenerative chronic joint disease. Although OA seriously affects the quality of life of patients, no effective treatment options are provided so far. Fibroblast growth factor sig-naling pathway is not only involved in regulating normal physiological processes, but also related to the occurrence and development of osteoarthritis, especially in cartilage metabolism and synthesis. In this review, recent studies about FGF/FGFR signaling pathway in the development of osteoarthri-tis, the mechanism of cartilage and subchondral bone degeneration, and the treatment of osteoar-thritis related to this pathway were summarized.
文章引用:何子轩, 陈海啸. 成纤维细胞生长因子在骨关节炎的研究进展[J]. 临床医学进展, 2023, 13(2): 2543-2549. https://doi.org/10.12677/ACM.2023.132359

参考文献

[1] Bannuru, R.R., Osani, M.C., Vaysbrot, E.E., et al. (2019) OARSI Guidelines for the Non-Surgical Management of Knee, Hip, and Polyarticular Osteoarthritis. Osteoarthritis and Cartilage, 27, 1578-1589. [Google Scholar] [CrossRef] [PubMed]
[2] Metcalfe, D., Perry, D.C., Claireaux, H.A., et al. (2019) Does This Patient Have Hip Osteoarthritis? The Rational Clinical Examination Systematic Review. JAMA, 322, 2323. [Google Scholar] [CrossRef] [PubMed]
[3] Kolasinski, S.L., Neogi, T., Hochberg, M.C., et al. (2020) 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis & Rheumatology, 72, 220-233. [Google Scholar] [CrossRef] [PubMed]
[4] Beenken, A. and Mohammadi, M. (2009) The FGF Family: Biology, Path-ophysiology and Therapy. Nature Reviews Drug Discovery, 8, 235-253. [Google Scholar] [CrossRef] [PubMed]
[5] Nishimura, R., Hata, K., Takahata, Y., et al. (2020) Role of Signal Transduc-tion Pathways and Transcription Factors in Cartilage and Joint Diseases. International Journal of Molecular Sciences, 21, 1340. [Google Scholar] [CrossRef] [PubMed]
[6] Itoh, N. and Ornitz, D.M. (2011) Fibroblast Growth Factors: From Molecular Evolution to Roles in Development, Metabolism and Disease. Journal of Biochemistry, 149, 121-130. [Google Scholar] [CrossRef] [PubMed]
[7] Ornitz, D.M., Itoh, N. (2015) The Fibroblast Growth Factor Signaling Pathway. WIREs Developmental Biology, 4, 215-266. [Google Scholar] [CrossRef] [PubMed]
[8] Gotoh, N. (2008) Regulation of Growth Factor Signaling by FRS2 Family Docking/Scaffold Adaptor Proteins. Cancer Science, 99, 1319-1325. [Google Scholar] [CrossRef] [PubMed]
[9] Krejci, P., Masri, B., Salazar, L., et al. (2007) Bisindol-ylmaleimide I Suppresses Fibroblast Growth Factor-Mediated Activation of Erk MAP Kinase in Chondrocytes by Pre-venting Shp2 Association with the Frs2 and Gab1 Adaptor Proteins. Journal of Biological Chemistry, 282, 2929-2936. [Google Scholar] [CrossRef
[10] Ong, S.H., Hadari, Y.R., Gotoh, N., et al. (2001) Stimulation of Phosphatidylinositol 3-Kinase by Fibroblast Growth Factor Receptors Is Mediated by Coordinated Recruitment of Multi-ple Docking Proteins. Proceedings of the National Academy of Sciences, 98, 6074-6079. [Google Scholar] [CrossRef] [PubMed]
[11] Yan, D., Chen, D., Cool, S.M., et al. (2011) Fibroblast Growth Fac-tor Receptor 1 Is Principally Responsible for Fibroblast Growth Factor 2-Induced Catabolic Activities in Human Articu-lar Chondrocytes. Arthritis Research & Therapy, 13, R130. [Google Scholar] [CrossRef] [PubMed]
[12] Ellman, M.B., Yan, D., Ahmadinia, K., et al. (2013) Fibroblast Growth Factor Control of Cartilage Homeostasis. Journal of Cellular Bio-chemistry, 114, 735-742. [Google Scholar] [CrossRef] [PubMed]
[13] Xu, W., Xie, Y., Wang, Q., et al. (2016) A Novel Fibroblast Growth Factor Receptor 1 Inhibitor Protects against Cartilage Degradation in a Murine Model of Osteoarthritis. Scientific Reports, 6, Article No. 24042. [Google Scholar] [CrossRef] [PubMed]
[14] Weng, T., Yi, L., Huang, J., et al. (2012) Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee Cartilage Attenuates the Degeneration of Articular Cartilage in Adult Mice. Arthritis & Rheumatism, 64, 3982-3992. [Google Scholar] [CrossRef] [PubMed]
[15] Wang, Z., Huang, J., Zhou, S., et al. (2018) Loss of Fgfr1 in Chondrocytes Inhibits Osteoarthritis by Promoting Autophagic Activity in Temporomandibular Joint. Journal of Biological Chemistry, 293, 8761-8774. [Google Scholar] [CrossRef
[16] Li, X., Ellman, M.B., Kroin, J.S., et al. (2012) Species-Specific Biological Effects of FGF-2 in Articular Cartilage: Implication for Distinct Roles within the FGF Receptor Family. Jour-nal of Cellular Biochemistry, 113, 2532-2542. [Google Scholar] [CrossRef] [PubMed]
[17] Valverde-Franco, G. (2003) Defective Bone Mineralization and Osteopenia in Young Adult FGFR3-/- Mice. Human Molecular Genetics, 13, 271-284. [Google Scholar] [CrossRef] [PubMed]
[18] Tang, J., Su, N., Zhou, S., et al. (2016) Fibroblast Growth Factor Recep-tor 3 Inhibits Osteoarthritis Progression in the Knee Joints of Adult Mice: FGFR-3 Protects Articular Cartilage against Degeneration. Arthritis & Rheumatology, 68, 2432-2443. [Google Scholar] [CrossRef] [PubMed]
[19] Zhou, S., Xie, Y., Li, W., et al. (2016) Conditional Deletion of Fgfr3 in Chondrocytes Leads to Osteoarthritis-Like Defects in Temporo-mandibular Joint of Adult Mice. Scientific Reports, 6, Article No. 24039. [Google Scholar] [CrossRef] [PubMed]
[20] Kuang, L., Wu, J., Su, N., Qi, H., Chen, H., et al. (2020) FGFR3 Defi-ciency Enhances CXCL12-Dependent Chemotaxis of Macrophages via Upregulating CXCR7 and Aggravates Joint De-struction in Mice. Annals of Rheumatic Diseases, 79, 112-122. [Google Scholar] [CrossRef] [PubMed]
[21] Sahni, M., Ambrosetti, D.C., Mansukhani, A., et al. (1999) FGF Signaling Inhibits Chondrocyte Proliferation and Regulates Bone Development through the STAT-1 Pathway. Genes & Development, 13, 1361-1366. [Google Scholar] [CrossRef] [PubMed]
[22] Li, R., Wang, B., He, C.Q., et al. (2015) Upregulation of Fibroblast Growth Factor 1 in the Synovial Membranes of Patients with Late Stage Osteoarthritis. Genetics and Molecular Research, 14, 11191-11199. [Google Scholar] [CrossRef
[23] Nishida, T., Kubota, S., Fukunaga, T., et al. (2003) CTGF/Hcs24, Hypertrophic Chondrocyte-Specific Gene Product, Interacts with Perlecan in Regulating the Proliferation and Differentiation of Chondrocytes. Journal of Cellular Physiology, 196, 265-275. [Google Scholar] [CrossRef] [PubMed]
[24] Abd El Kader, T., Kubota, S., Anno, K., et al. (2014) Direct Interaction be-tween CCN Family Protein 2 and Fibroblast Growth Factor 1. Journal of Cell Communication and Signaling, 8, 157-163. [Google Scholar] [CrossRef] [PubMed]
[25] El-Seoudi, A., Abd El Kader, T., Nishida, T., et al. (2017) Cata-bolic Effects of FGF-1 on Chondrocytes and Its Possible Role in Osteoarthritis. Journal of Cell Communication and Signaling, 11, 255-263. [Google Scholar] [CrossRef] [PubMed]
[26] Vincent, T., Hermansson, M., Bolton, M., et al. (2002) Basic FGF Mediates an Immediate Response of Articular Cartilage to Mechanical Injury. Proceedings of the National Academy of Sciences, 99, 8259-8264. [Google Scholar] [CrossRef] [PubMed]
[27] Im, H.J., Muddasani, P., Natarajan, V., et al. (2007) Basic Fibroblast Growth Factor Stimulates Matrix Metalloproteinase-13 via the Molecular Cross-Talk between the Mitogen-Activated Protein Kinases and Protein Kinase Cδ Pathways in Human Adult Articular Chondrocytes. Journal of Biological Chem-istry, 282, 11110-11121. [Google Scholar] [CrossRef
[28] Muddasani, P., Norman, J.C., Ellman, M., et al. (2007) Basic Fibro-blast Growth Factor Activates the MAPK and NFκB Pathways That Converge on Elk-1 to Control Production of Matrix Metalloproteinase-13 by Human Adult Articular Chondrocytes. Journal of Biological Chemistry, 282, 31409-31421. [Google Scholar] [CrossRef
[29] Sawaji, Y., Hynes, J., Vincent, T., et al. (2008) Fibroblast Growth Factor 2 Inhibits Induction of Aggrecanase Activity in Human Articular Cartilage. Arthritis & Rheumatism, 58, 3498-3509. [Google Scholar] [CrossRef] [PubMed]
[30] Chong, K., Chanalaris, A., Burleigh, A., et al. (2013) Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage in Vitro and in Vivo. Arthritis & Rheumatism, 65, 2346-2355. [Google Scholar] [CrossRef] [PubMed]
[31] Chia, S.L., Sawaji, Y., Burleigh, A., et al. (2009) Fibroblast Growth Factor 2 Is an Intrinsic Chondroprotective Agent That Suppresses ADAMTS-5 and Delays Cartilage Degradation in Murine Osteoarthritis. Arthritis & Rheumatism, 60, 2019-2027. [Google Scholar] [CrossRef] [PubMed]
[32] Schmidt, L., Taiyab, A., Melvin, V.S., et al. (2018) Increased FGF8 Signaling Promotes Chondrogenic Rather than Osteogenic Development in the Embryonic Skull. Disease Models & Mechanisms, 11, dmm.031526. [Google Scholar] [CrossRef] [PubMed]
[33] Uchii, M., Tamura, T., Suda, T., et al. (2008) The Role of Fibroblast Growth Factor-8 (FGF8) in Animal Models of Osteoarthritis. Arthritis Research & Therapy, 10, R90. [Google Scholar] [CrossRef] [PubMed]
[34] Pei, W., Huang, X., Ni, B., et al. (2021) Selective STAT3 Inhibitor Alantolac-tone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis. Frontiers in Phar-macology, 12, Article ID: 730312. [Google Scholar] [CrossRef] [PubMed]
[35] Ellsworth, J.L., Berry, J., Bukowski, T., et al. (2002) Fibroblast Growth Factor-18 Is a Trophic Factor for Mature Chondrocytes and Their Progenitors. Osteoarthritis and Cartilage, 10, 308-320. [Google Scholar] [CrossRef] [PubMed]
[36] Moore, E.E., Bendele, A.M., Thompson, D.L., et al. (2005) Fibroblast Growth Factor-18 Stimulates Chondrogenesis and Cartilage Repair in a Rat Model of Injury-Induced Osteoarthritis. Os-teoarthritis and Cartilage, 13, 623-631. [Google Scholar] [CrossRef] [PubMed]
[37] Mori, Y., Saito, T., Chang, S.H., et al. (2014) Identification of Fi-broblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling. Journal of Biological Chemistry, 289, 10192-10200. [Google Scholar] [CrossRef
[38] Li, X., An, H.S., Ellman, M., et al. (2008) Action of Fibroblast Growth Factor-2 on the Intervertebral Disc. Arthritis Research & Therapy, 10, R48. [Google Scholar] [CrossRef] [PubMed]
[39] Lohmander, L.S., Hellot, S., Dreher, D., et al. (2014) Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double-Blind, Place-bo-Controlled Trial: Sprifermin Effects in Knee Osteoarthritis. Arthritis & Rheumatology, 66, 1820-1831. [Google Scholar] [CrossRef] [PubMed]