臺灣博碩士論文加值系統

纖維肌痛症 (Fibromyalgia, FM) 是一種慢性且造成患者全身廣泛性疼痛的疾病，症狀包含頭痛、疲倦、睡眠障礙及憂鬱等等。目前診斷方式主要依靠問卷來對病人進行評估，臨床上並沒有可以作為診斷 FM 的生物標記物 (Biomarker)，因此難以客觀判斷。骨關節炎 (Osteoarthritis, OA) 也是常見的慢性疾病之一，其症狀包含關節疼痛、腫脹及僵硬等等，診斷方式以臨床症狀及 X 光作為依據，但卻難以早期發現早期治療。目前對於 FM 及 OA 的致病成因仍然不清楚。近年來，隨著質譜技術的蓬勃發展，許多蛋白質體相關研究會搭配質譜儀 (Mass spectrometry, MS) 進行分析，研究生物體內生理狀態和代謝作用之交互作用。本研究透過高效液相層析儀搭配四極桿暨飛行時間式質譜儀 (Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry, UPLC-Q-TOF MS) 以及非數據依賴擷取之質譜定量技術 SWATH (Sequential window acquisition of all theoretical fragment ion spectra) 針對 FM 及 OA 患者的尿液進行蛋白質體學 (Proteomics) 的分析，旨在探討 FM 及 OA 對人體蛋白質的影響，找出相關致病機制及致病路徑，做為早期診斷或治療的生物標記物。分析結果以 p-value < 0.05 且 Fold change > 1.5 或 < 0.67 作為篩選差異表現蛋白的標準，計算完後，FM 組別與 Healthy control (HC) 相比有 54 個差異表現蛋白；OA 組別與 HC 相比有 17 個差異表現蛋白；FM 組別與 OA 組別相比有 47 個差異表現蛋白。在路徑分析結果表明 FM 與 OA 組別中的差異表達蛋白大多參與凝血和補體系統相關路徑、血清素作用路徑、多巴胺作用路徑、麩胺酸作用路徑及急性期反應，這些路徑與發炎反應及神經系統異常相關，本實驗透過蛋白質體學的角度發現 FM 及 OA 造成發炎反應，會使急性期蛋白顯著上升表達，GNB2 顯著下降表達，藉以區分健康及罹患疾病，再透過凝血和補體系統中的 SERPING1 及 EPCR 來區分 FM 及 OA ，透過這些路經更加了解 FM 及 OA 對人體蛋白質之影響。

Fibromyalgia (FM) is a chronic widespread pain disorder that commonly includes generalized chronic pain, fatigue, depression and sleep disturbance. In the clinic, there is no biomarker that can be used to distinguish fibromyalgia, which makes it difficult to diagnose. Osteoarthritis (OA) is one of the common chronic diseases in the world with its main symptoms including joint pain and joint stiffness. So far, the causes of FM and OA have been unclear but both have had the same symptoms of joint pain and stiffness. Therefore, finding biomarkers for diagnosis is urgently needed. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) is a label-free mass spectrometry quantitative technique, which can retain complete fragment ion data and has good accuracy as well as reproducibility. In this study, SWATH-MS is used to analyze the proteome in urine samples of FM and OA patients to investigate the mechanisms of FM and OA. In terms of results, the differential expression proteins between samples and wild type were screened by p-value < 0.05 and fold change > 1.5 or < 0.67. After calculation, FM group has 54 differentially expressed proteins compared with HC; OA group has 17 differentially expressed proteins compared with HC; FM group has 47 differentially expressed proteins compared with OA group. Functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis resulted in the differentially expressed proteins in the FM and OA groups are mostly involved in the coagulation and complement system-related pathways, serotonin pathways, dopamine pathways, glutamate pathways and acute phase reactions. These pathways are related to inflammation and neurological abnormalities. Through these pathways, we can better understand the effects of FM and OA on human proteome.

中文摘要 i
Abstract ii
目次 iii
附圖目次 vi
圖目次 viii
表目次 x
英文縮寫對照表 xi
第一章 緒論 1
第一節 前言 1
第二節 纖維肌痛症 (Fibromyalgia, FM) 3
2.1 FM 介紹 3
2.2 流行病學 3
2.3 FM 之臨床症狀 4
2.3.1 疼痛 (Pain) 4
2.3.2 疲勞 (Fatigue) 5
2.3.3 認知能力 (Cognitive ability) 5
2.3.4 睡眠障礙 (Sleep disorder) 5
2.3.5 內分泌失調 (Endocrine disorders) 5
2.4 FM 之致病成因 6
2.4.1 中樞神經系統異常 (Central nervous system abnormalities) 6
2.4.2 遺傳 (Inheritance) 7
2.4.3 心理創傷 (Psychological trauma) 8
2.4.4 睡眠障礙 (Sleep disorder) 9
2.4.5 外傷 (Trauma) 9
2.5 FM 之臨床診斷 10
2.6 FM 之治療 15
2.6.1 藥物治療 (Pharmacologic treatment) 15
2.6.2 非藥物治療 (Nonpharmacologic treatment) 18
2.7 質譜於 FM 之研究 20
第三節 骨關節炎 (Osteoarthritis, OA) 21
3.1 OA 介紹 21
3.2 流行病學 21
3.3 OA 之臨床症狀 22
3.4 OA 之致病成因 22
3.4.1 遺傳 (Inheritance) 23
3.4.2 性別 (Sex) 24
3.4.3 受傷 (Trauma) 25
3.4.4 生活方式 (Lifestyle) 25
3.5 OA 之臨床診斷 26
3.6 OA 之治療 27
3.6.1 藥物治療 (pharmacologic treatment) 27
3.6.2 非藥物治療 (Nonpharmacologic treatment) 30
3.6.3 手術治療 (Surgical treatment) 31
3.7 質譜於 OA 之研究 33
第四節 蛋白質體學 (Proteomics) 34
第五節 研究動機 39
第六節 實驗流程 40
第二章 材料與方法 41
第一節 尿液真實樣品收集 41
第二節 尿液蛋白質萃取 (Urine protein extraction) 41
第三節 蛋白質定量 (Protein quantification) 42
第四節 十二烷基硫酸鈉聚丙烯醯胺凝膠電泳 (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis, SDS-PAGE) 42
4.1 11% SDS-PAGE 43
4.2 28% SDS-PAGE 43
第五節 銀染 (Silver staining) 44
第六節 膠體內酵素水解 (In-gel digestion) 45
第七節 Zip-Tip 去鹽純化 45
第八節 液相層析串聯式質譜儀分析 (LC-MS/MS analysis) 46
8.1 液相層析串聯質譜儀 (LC-MS/MS) 46
8.2 層析梯度條件測試 46
8.3 酵素水解濃度測試 48
8.4 內標準品濃度測試 48
8.5 樣品上機量測試 48
8.6 儀器狀態之標準品測試 48
8.6.1 Beta-galactosidase (β-gal) 48
8.6.2 Escherichia coli (E. coli) 49
8.7 尿液蛋白真實樣品上機 49
8.7.1 Data-dependent acquisition (DDA) 49
8.7.2 Data-independent acquisition (DIA) 50
第九節 以 Protein PilotTM Software 進行蛋白質身分鑑定 51
第十節 以 PeakView® 2.1 Software 進行蛋白質定量 52
第十一節 化學計量學分析 (Chemometrics analysis) 53
11.1 主成分分析 (Principal component analysis, PCA) 53
11.2 結構正交投影辨別分析法 (Orthogonal projections to latent structure discriminant analysis, OPLS-DA) 53
第十二節 蛋白質功能性分析 (Gene ontology analysis, GO analysis) 54
第十三節 KEGG 路徑分析 54
第三章 結果與討論 55
第一節 蛋白質定量結果 55
第二節 11% SDS-PAGE 55
第三節 28% Stacking gel 55
第四節 液相層析串聯式質譜分析 (LC-MS/MS) 56
4.1 前處理及上機條件最佳化 56
4.2 尿液蛋白真實樣品上機 57
4.2.1 DDA 之 Ion library 建立 57
4.2.2 SWATH variable window 分析 57
第五節 化學計量學分析 58
第六節 蛋白質功能性分析 61
第七節 KEGG 路徑分析 62
第八節 發炎因子 68
第四章 結論 69
參考文獻 123

1.Sarzi-Puttini, P., et al., Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nature reviews. Rheumatology 2020, 16 (11), 645-660.
2.Wolfe, F., et al., 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Seminars in arthritis and rheumatism 2016, 46 (3), 319-329.
3.Hochberg, M. C., et al., American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis care & research 2012, 64 (4), 465-474.
4.Jin, L. K., et al., [Study on the correlation between syndrome differ classification of knee osteoarthritis and X-ray image]. Zhongguo gu shang = China journal of orthopaedics and traumatology 2010, 23 (12), 906-9.
5.Wasinger, V. C., et al., Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis 1995, 16 (7), 1090-4.
6.Jones, A. W., et al., Dissociation techniques in mass spectrometry-based proteomics. The Analyst 2011, 136 (17), 3419-29.
7.Gillet, L. C., et al., Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Molecular & cellular proteomics : MCP 2012, 11 (6), O111.016717.
8.Sumpton, J. E., et al., Fibromyalgia. Handbook of clinical neurology 2014, 119, 513-27.
9.Ruhmann, W., The earliest book on rheumatism. Br J Rheumatol 1940, 2:140–162.
10.Gowers, W. R., A Lecture on Lumbago: Its Lessons and Analogues: Delivered at the National Hospital for the Paralysed and Epileptic. British medical journal 1904, 1 (2246), 117-21.
11.Inanici, F., et al., History of fibromyalgia: past to present. Current pain and headache reports 2004, 8 (5), 369-78.
12.Hench, P. K., Twenty-second rheumatism review. Review of the American and English literature for the years 1973 and 1974. Arthritis and rheumatism 1976, 19 (6 suppl), 1081–1089.
13.Smythe, H. A., et al., Two contributions to understanding of the "fibrositis" syndrome. Bulletin on the rheumatic diseases 1977, 28 (1), 928-31.
14.Wolfe, F., Fibromyalgia. Rheumatic diseases clinics of North America 1990, 16 (3), 681-98.
15.Gui, M. S., et al., Temporomandibular disorders in fibromyalgia syndrome: a short-communication. Revista Brasileira de Reumatologia (English Edition) 2015, 55 (2), 189-194.
16.De Tommaso, M., et al., Clinical features of headache patients with fibromyalgia comorbidity. The Journal of Headache and Pain 2011, 12 (6), 629-638.
17.Koroschetz, J., et al., Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia. BMC Neurology 2011, 11 (1), 55.
18.Johnson, C. M., et al., Fibromyalgia and Irritable Bowel Syndrome in Female Pelvic Pain. Seminars in reproductive medicine 2018, 36 (2), 136-142.
19.Wolfe, F., et al., The prevalence and meaning of fatigue in rheumatic disease. The Journal of rheumatology 1996, 23 (8), 1407-17.
20.Galvez-Sánchez, C. M., et al., Cognitive Impairments in Fibromyalgia Syndrome: Associations With Positive and Negative Affect, Alexithymia, Pain Catastrophizing and Self-Esteem. Front Psychol 2018, 9, 377-377.
21.Glass, J. M., et al., Cognitive dysfunction in fibromyalgia. Current rheumatology reports 2001, 3 (2), 123-7.
22.Keskindag, B., et al., The association between pain and sleep in fibromyalgia. Saudi medical journal 2017, 38 (5), 465-475.
23.Choy, E. H., The role of sleep in pain and fibromyalgia. Nature reviews. Rheumatology 2015, 11 (9), 513-20.
24.Rossi, A., et al., Fibromyalgia and nutrition: what news? Clinical and experimental rheumatology 2015, 33 (1 Suppl 88), S117-25.
25.Geenen, R., et al., Evaluation and management of endocrine dysfunction in fibromyalgia. Rheumatic diseases clinics of North America 2002, 28 (2), 389-404.
26.Baek, S. H., et al., Lengthened Cutaneous Silent Period in Fibromyalgia Suggesting Central Sensitization as a Pathogenesis. PloS one 2016, 11 (2), e0149248.
27.Russell, I. J., et al., Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis and rheumatism 1992, 35 (5), 550-6.
28.Jensen, K. B., et al., Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain 2009, 144 (1-2), 95-100.
29.Clauw, D. J., Fibromyalgia and Related Conditions. Mayo Clinic Proceedings 2015, 90 (5), 680-692.
30.Mogil, J. S., Pain genetics: past, present and future. Trends in genetics : TIG 2012, 28 (6), 258-66.
31.Pellegrino, M. J., et al., Familial occurrence of primary fibromyalgia. Archives of physical medicine and rehabilitation 1989, 70 (1), 61-3.
32.Buskila, D., et al., Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM. The Journal of rheumatology 1997, 24 (5), 941-4.
33.Buskila, D., et al., Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome. Arthritis research & therapy 2006, 8 (5), 218.
34.Park, D. J., et al., New insights into the genetics of fibromyalgia. The Korean journal of internal medicine 2017, 32 (6), 984-995.
35.Pieritz, K., et al., Childhood adversities and laboratory pain perception. Neuropsychiatric disease and treatment 2015, 11, 2109-16.
36.Weissbecker, I., et al., Childhood trauma and diurnal cortisol disruption in fibromyalgia syndrome. Psychoneuroendocrinology 2006, 31 (3), 312-24.
37.Häuser, W., et al., Posttraumatic stress disorder in fibromyalgia syndrome: prevalence, temporal relationship between posttraumatic stress and fibromyalgia symptoms, and impact on clinical outcome. Pain 2013, 154 (8), 1216-23.
38.Cleare, A. J., Stress and fibromyalgia--what is the link? Journal of psychosomatic research 2004, 57 (5), 423-5.
39.Gupta, A., et al., Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link. Arthritis research & therapy 2004, 6 (3), 98-106.
40.Lentz, M. J., et al., Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women. The Journal of rheumatology 1999, 26 (7), 1586-92.
41.Older, S. A., et al., The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I. The Journal of rheumatology 1998, 25 (6), 1180-6.
42.Buskila, D., et al., Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury. Arthritis and rheumatism 1997, 40 (3), 446-52.
43.Bennett, R. M., et al., An internet survey of 2,596 people with fibromyalgia. BMC musculoskeletal disorders 2007, 8, 27.
44.Wolfe, F., et al., The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis care & research 2010, 62 (5), 600-10.
45.De Sanctis, V., et al., The juvenile fibromyalgia syndrome (JFMS): a poorly defined disorder. Acta bio-medica : Atenei Parmensis 2019, 90 (1), 134-148.
46.Burckhardt, C. S., et al., The fibromyalgia impact questionnaire: development and validation. The Journal of rheumatology 1991, 18 (5), 728-33.
47.Bennett, R. M., et al., The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties. Arthritis research & therapy 2009, 11 (4), R120.
48.Russell, I. J., Fibromyalgia syndrome: approach to management. CNS spectrums 2008, 13 (3 Suppl 5), 27-33.
49.Abeles, M., et al., Update on fibromyalgia therapy. The American journal of medicine 2008, 121 (7), 555-61.
50.Chinn, S., et al., Fibromyalgia Pathogenesis and Treatment Options Update. Current pain and headache reports 2016, 20 (4), 25.
51.Edward, M., et al., Treatment Approaches for Fibromyalgia. US Pharm. 2021, . 2021;46(3):17-22.
52.Shim, J. H., Clinical application of a2-d ligand. Hanyang Med Rev 2011, ;31:55–62.
53.Nasser, K., et al., Twice daily versus once nightly dosing of pregabalin for fibromyalgia: a double-blind randomized clinical trial of efficacy and safety. Arthritis care & research 2014, 66 (2), 293-300.
54.Rico-Villademoros, F., et al., Amitriptyline for the treatment of fibromyalgia: a comprehensive review. Expert review of neurotherapeutics 2015, 15 (10), 1123-50.
55.Aswal, N., et al., Study on Antidepressant Drug to Cure Depression. Journal of Formulation Science & Bioavailability 2018, 2:1.
56.Moore, R. A., et al., Amitriptyline for fibromyalgia in adults. Cochrane Database of Systematic Reviews 2015, (7).
57.Çapaci, K., et al., Comparison of the effects of amitriptyline and paroxetine in the treatment of fibromyalgia syndrome. the pain clinic 2013, 223-228.
58.Gałecki, P., et al., The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs. Progress in neuro-psychopharmacology & biological psychiatry 2018, 80 (Pt C), 291-294.
59.Arnold, L. M., et al., A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. The American journal of medicine 2002, 112 (3), 191-7.
60.Dadabhoy, D., et al., Therapy Insight: fibromyalgia--a different type of pain needing a different type of treatment. Nature clinical practice. Rheumatology 2006, 2 (7), 364-72.
61.Arnold, L. M., et al., A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder. Pain 2005, 119 (1-3), 5-15.
62.Vitton, O., et al., A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Human psychopharmacology 2004, 19 Suppl 1, S27-35.
63.Macfarlane, G. J., et al., EULAR revised recommendations for the management of fibromyalgia. Annals of the rheumatic diseases 2017, 76 (2), 318-328.
64.Thieme, K., et al., Evidenced-Based Guidelines on the Treatment of Fibromyalgia Patients: Are They Consistent and If Not, Why Not? Have Effective Psychological Treatments Been Overlooked? The journal of pain : official journal of the American Pain Society 2017, 18 (7), 747-756.
65.Góes, S. M., et al., Functional capacity, muscle strength and falls in women with fibromyalgia. Clinical biomechanics (Bristol, Avon) 2012, 27 (6), 578-83.
66.El-Shewy, K. M., et al., Hyperbaric oxygen and aerobic exercise in the long-term treatment of fibromyalgia: A narrative review. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2019, 109, 629-638.
67.Busch, A. J., et al., Resistance exercise training for fibromyalgia. The Cochrane database of systematic reviews 2013, 2013 (12), Cd010884.
68.Vas, J., et al., Acupuncture for fibromyalgia in primary care: a randomised controlled trial. Acupuncture in medicine : journal of the British Medical Acupuncture Society 2016, 34 (4), 257-66.
69.Deare, J. C., et al., Acupuncture for treating fibromyalgia. The Cochrane database of systematic reviews 2013, 2013 (5), Cd007070.
70.Lazaridou, A., et al., Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia. The Clinical journal of pain 2017, 33 (3), 215-221.
71.Paz, C., et al., Personal Construct Therapy vs Cognitive Behavioral Therapy in the Treatment of Depression in Women with Fibromyalgia: Study Protocol for a Multicenter Randomized Controlled Trial. Neuropsychiatric disease and treatment 2020, 16, 301-311.
72.Baraniuk, J. N., et al., A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid. BMC Neurol 2005, 5, 22.
73.Bazzichi, L., et al., Detection of potential markers of primary fibromyalgia syndrome in human saliva. Proteomics. Clinical applications 2009, 3 (11), 1296-304.
74.Malatji, B. G., et al., The GC-MS metabolomics signature in patients with fibromyalgia syndrome directs to dysbiosis as an aspect contributing factor of FMS pathophysiology. Metabolomics : Official journal of the Metabolomic Society 2019, 15 (4), 54.
75.Clos-Garcia, M., et al., Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia. EBioMedicine 2019, 46, 499-511.
76.Willy, C., et al., Richard von Volkmann: surgeon and Renaissance man. Clinical orthopaedics and related research 2008, 466 (2), 500-6.
77.Safiri, S., et al., Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017. Annals of the rheumatic diseases 2020, 79 (6), 819-828.
78.Hunter, D. J., et al., Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet (London, England) 2020, 396 (10264), 1711-1712.
79.Felson, D. T., et al., Osteoarthritis: new insights. Part 1: the disease and its risk factors. Annals of internal medicine 2000, 133 (8), 635-46.
80.Haq, S. A., et al., Osteoarthritis of the knees in the COPCORD world. International journal of rheumatic diseases 2011, 14 (2), 122-9.
81.Dagenais, S., et al., Systematic review of the prevalence of radiographic primary hip osteoarthritis. Clinical orthopaedics and related research 2009, 467 (3), 623-37.
82.Hu, Q., et al., Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. International journal of molecular sciences 2021, 22 (4).
83.Spector, T. D., et al., Genetic influences on osteoarthritis in women: a twin study. BMJ (Clinical research ed.) 1996, 312 (7036), 940-3.
84.Fathollahi, A., et al., Epigenetics in osteoarthritis: Novel spotlight. Journal of cellular physiology 2019, 234 (8), 12309-12324.
85.Tachmazidou, I., et al., Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nature genetics 2019, 51 (2), 230-236.
86.Reynard, L. N., et al., Osteoarthritis year in review 2019: genetics, genomics and epigenetics. Osteoarthritis and cartilage 2020, 28 (3), 275-284.
87.Prieto-Alhambra, D., et al., Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Annals of the rheumatic diseases 2014, 73 (9), 1659-1664.
88.Sowers, M. R., et al., Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis and rheumatism 2006, 54 (8), 2481-7.
89.Son, Y. O., et al., Estrogen-related receptor γ causes osteoarthritis by upregulating extracellular matrix-degrading enzymes. Nature communications 2017, 8 (1), 2133.
90.Long, M. J., et al., Predicting knee osteoarthritis risk in injured populations. Clinical biomechanics (Bristol, Avon) 2017, 47, 87-95.
91.Jiang, L., et al., Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint bone spine 2012, 79 (3), 291-7.
92.Conde, J., et al., Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis 2011, 2011, 203901.
93.Johnson, V. L., et al., The epidemiology of osteoarthritis. Best practice & research. Clinical rheumatology 2014, 28 (1), 5-15.
94.Altman, R., et al., The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis and rheumatism 1990, 33 (11), 1601-10.
95.MacDonald, C. W., et al., Clinical outcomes following manual physical therapy and exercise for hip osteoarthritis: A case series. The Journal of orthopaedic and sports physical therapy 2006, 36 (8), 588-99.
96.Hunter, D. J., et al., Seminar Osteoarthritis. 2019.
97.Dragos, D., et al., Phytomedicine in Joint Disorders. Nutrients 2017, 9 (1).
98.Carreira, A. C., et al., Bone morphogenetic proteins: facts, challenges, and future perspectives. Journal of dental research 2014, 93 (4), 335-45.
99.Hunter, D. J., et al., Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC musculoskeletal disorders 2010, 11 (1), 232.
100.Knop, E., et al., Platelet-rich plasma for osteoarthritis treatment. Revista brasileira de reumatologia 2016, 56 (2), 152-64.
101.Kon, E., et al., Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 2010, 18 (4), 472-9.
102.Spaková, T., et al., Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. American journal of physical medicine & rehabilitation 2012, 91 (5), 411-7.
103.Gigout, A., et al., Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix. Osteoarthritis and cartilage 2017, 25 (11), 1858-1867.
104.Yao, X., et al., Fibroblast growth factor 18 exerts anti-osteoarthritic effects through PI3K-AKT signaling and mitochondrial fusion and fission. Pharmacological research 2019, 139, 314-324.
105.Lohmander, L. S., et al., Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis & rheumatology (Hoboken, N.J.) 2014, 66 (7), 1820-31.
106.Wei-yue, G., et al., Fibroblast Growth Factor and Bone Related Diseases[J]. . CHINA BIOTECHNOLOGY 2016, 36(8): 99-104.
107.Pittenger, M. F., et al., Multilineage potential of adult human mesenchymal stem cells. Science (New York, N.Y.) 1999, 284 (5411), 143-7.
108.Prockop, D. J., et al., Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Molecular therapy : the journal of the American Society of Gene Therapy 2012, 20 (1), 14-20.
109.Manferdini, C., et al., Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis and rheumatism 2013, 65 (5), 1271-81.
110.Orozco, L., et al., Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 2013, 95 (12), 1535-41.
111.Vangsness, C. T., Jr., et al., Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. The Journal of bone and joint surgery. American volume 2014, 96 (2), 90-8.
112.Bruyère, O., et al., An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Seminars in arthritis and rheumatism 2019, 49 (3), 337-350.
113.Messier, S. P., et al., Intentional Weight Loss in Overweight and Obese Patients With Knee Osteoarthritis: Is More Better? Arthritis care & research 2018, 70 (11), 1569-1575.
114.Sato, M., et al., Combined surgery and chondrocyte cell-sheet transplantation improves clinical and structural outcomes in knee osteoarthritis. NPJ Regenerative medicine 2019, 4, 4.
115.Moseley, J. B., et al., A controlled trial of arthroscopic surgery for osteoarthritis of the knee. The New England journal of medicine 2002, 347 (2), 81-8.
116.Thorlund, J. B., et al., Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. BMJ (Clinical research ed.) 2015, 350, h2747.
117.Brouwer, R. W., et al., Osteotomy for treating knee osteoarthritis. The Cochrane database of systematic reviews 2005, (1), Cd004019.
118.Hermansson, M., et al., Proteomic analysis of articular cartilage shows increased type II collagen synthesis in osteoarthritis and expression of inhibin betaA (activin A), a regulatory molecule for chondrocytes. The Journal of biological chemistry 2004, 279 (42), 43514-21.
119.Wu, J., et al., Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis. Arthritis and rheumatism 2007, 56 (11), 3675-84.
120.Wang, B., et al., Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage. Archives of pharmacal research 2014, 37 (6), 793-802.
121.Luo, H., et al., Liquid chromatography-mass spectrometry-based quantitative proteomics analysis reveals chondroprotective effects of astragaloside IV in interleukin-1β-induced SW1353 chondrocyte-like cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017, 91, 796-802.
122.Shumate, C. B., et al., Coronaspray nebulization and ionization of liquid samples for ion mobility spectrometry. Analytical chemistry 1989, 61 (6), 601-6.
123.Fenn, J. B., et al., Electrospray ionization for mass spectrometry of large biomolecules. Science (New York, N.Y.) 1989, 246 (4926), 64-71.
124.Karas, M., et al., Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Analytical chemistry 1988, 60 (20), 2299-301.
125.Vogeser, M., et al., A decade of HPLC-MS/MS in the routine clinical laboratory--goals for further developments. Clinical biochemistry 2008, 41 (9), 649-62.
126.Woods, A. G., et al., Mass spectrometry for proteomics-based investigation. Advances in experimental medicine and biology 2014, 806, 1-32.
127.Ross, P. L., et al., Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Molecular & cellular proteomics : MCP 2004, 3 (12), 1154-69.
128.Zhu, W., et al., Mass spectrometry-based label-free quantitative proteomics. Journal of biomedicine & biotechnology 2010, 2010, 840518.
129.Wang, R., et al., Advancing untargeted metabolomics using data-independent acquisition mass spectrometry technology. Analytical and Bioanalytical Chemistry 2019, 411 (19), 4349-4357.
130.Lewandowska, A. E., et al., Qualitative and Quantitative Analysis of Proteome and Peptidome of Human Follicular Fluid Using Multiple Samples from Single Donor with LC-MS and SWATH Methodology. J Proteome Res 2017, 16 (8), 3053-3067.
131.Schlotterbeck, J., et al., Comprehensive MS/MS profiling by UHPLC-ESI-QTOF-MS/MS using SWATH data-independent acquisition for the study of platelet lipidomes in coronary artery disease. Analytica chimica acta 2019, 1046, 1-15.
132.Magistroni, R., et al., Proteomic analysis of urine from proteinuric patients shows a proteolitic activity directed against albumin. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2009, 24 (5), 1672-81.
133.Lee, R. S., et al., Optimizing Sample Handling for Urinary Proteomics. Journal of Proteome Research 2008, 7 (9), 4022-4030.
134.Chen, Y. Y., et al., A modified protein precipitation procedure for efficient removal of albumin from serum. Electrophoresis 2005, 26 (11), 2117-27.
135.Hao, R., et al., An Optimized Trichloroacetic Acid/Acetone Precipitation Method for Two-Dimensional Gel Electrophoresis Analysis of Qinchuan Cattle Longissimus Dorsi Muscle Containing High Proportion of Marbling. PloS one 2015, 10 (4), e0124723.
136.Collins, B. C., et al., Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry. Nature communications 2017, 8 (1).
137.Ma, C., et al., Terpenoid metabolic profiling analysis of transgenic Artemisia annua L. by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Metabolomics : Official journal of the Metabolomic Society 2009, 5 (4), 497-506.
138.Barnum, S. R., Complement in central nervous system inflammation. Immunologic research 2002, 26 (1-3), 7-13.
139.Heese, K., et al., Inflammatory signals induce neurotrophin expression in human microglial cells. Journal of neurochemistry 1998, 70 (2), 699-707.
140.Bae, J.-S., et al., Thrombin and activated protein C inhibit the expression of secretory group IIA phospholipase A2 in the TNF-α-activated endothelial cells by EPCR and PAR-1 dependent mechanisms. Thrombosis Research 2010, 125 (1), e9-e15.
141.M, M., et al., High In vivo Platelet Activity in Female Fibromyalgia Patients. Journal of Biomedical Sciencies 2016, 5 (3).
142.Aksu, K., et al., Inflammation-induced thrombosis: mechanisms, disease associations and management. Current pharmaceutical design 2012, 18 (11), 1478-93.
143.Ghosh, P., et al., The role of cartilage-derived antigens, pro-coagulant activity and fibrinolysis in the pathogenesis of osteoarthritis. Medical hypotheses 1993, 41 (2), 190-4.
144.Adayev, T., et al., The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha. Biochimica et biophysica acta 2003, 1640 (1), 85-96.
145.Haleem, D. J., Serotonin-1A receptor dependent modulation of pain and reward for improving therapy of chronic pain. Pharmacological research 2018, 134, 212-219.
146.Wood, P. B., et al., Fibromyalgia patients show an abnormal dopamine response to pain. The European journal of neuroscience 2007, 25 (12), 3576-82.
147.Holman, A. J., et al., A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis and rheumatism 2005, 52 (8), 2495-505.
148.Harris, R. E., Elevated excitatory neurotransmitter levels in the fibromyalgia brain. Arthritis research & therapy 2010, 12 (5), 141.
149.Bonnet, C. S., et al., AMPA/kainate glutamate receptor antagonists prevent posttraumatic osteoarthritis. JCI insight 2020, 5 (13).
150.Jackson, M. T., et al., Activation of cartilage matrix metalloproteinases by activated protein C. Arthritis & Rheumatism 2009, 60 (3), 780-791.
151.Riewald, M., et al., Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling. The Journal of biological chemistry 2005, 280 (20), 19808-14.
152.Gabay, C., et al., Acute-phase proteins and other systemic responses to inflammation. The New England journal of medicine 1999, 340 (6), 448-54.
153.Ramírez-Tejero, J. A., et al., Insight into the biological pathways underlying fibromyalgia by a proteomic approach. Journal of proteomics 2018, 186, 47-55.
154.Ritter, S. Y., et al., Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis and rheumatism 2013, 65 (4), 981-92.