Journal of Yeungnam Medical Science

Review article

The use of animal models in rheumatoid arthritis research: Jin-Sun Kong, Gi Heon Jeong, Seung-Ah Yoo; J Yeungnam Med Sci. 2023;40(1):23-29. Published online November 22, 2022; DOI: https://doi.org/10.12701/jyms.2022.00773

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The pathological hallmark of rheumatoid arthritis (RA) is a synovial pannus that comprises proliferating and invasive fibroblast-like synoviocytes, infiltrating inflammatory cells, and an associated neoangiogenic response. Animal models have been established to study these pathological features of human RA. Spontaneous and induced animal models of RA primarily reflect inflammatory aspects of the disease. Among various induced animal models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models are widely used to study the pathogenesis of RA. Improved transplantation techniques for severe combined immunodeficiency (SCID) mouse models of RA can be used to evaluate the effectiveness of potential therapeutics in human tissues and cells. This review provides basic information on various animal models of RA, including CIA and CAIA. In addition, we describe a SCID mouse coimplantation model that can measure the long-distance migration of human RA synoviocytes and cartilage destruction induced by these cells.

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CRISPRa engineered Elite macrophages enable adoptive cell therapy for rheumatoid arthritis
Yuhong Huang, Zhuqian Wang, Chuanxin Zhong, Hongzhen Chen, Xinxin Chen, Chunhao Cao, Fang Qiu, Duoli Xie, Jin Li, Jie Li, Xu Yang, Aiping Lu, Xuekun Fu, Chao Liang
The Innovation Medicine.2024; 2(1): 100050. CrossRef
Microenvironmental Enzyme-Responsive Methotrexate Modified Quercetin Micelles for the Treatment of Rheumatoid Arthritis
Xiuying Li, Xin Wang, Xiuwu Qu, Ningning Shi, Qinqing Li, Zhifang Yan, Yandong Li, Yingli Wang
International Journal of Nanomedicine.2024; Volume 19: 3259. CrossRef
Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review
James Perera, Chiara Aurora Delrosso, Alessandra Nerviani, Costantino Pitzalis
Cells.2024; 13(9): 743. CrossRef
Emerging Landscape of In Vitro Models for Assessing Rheumatoid Arthritis Management
Abhay Prakash Mishra, Rajesh Kumar, Seetha Harilal, Manisha Nigam, Deepanjan Datta, Sudarshan Singh
ACS Pharmacology & Translational Science.2024;[Epub] CrossRef

Original article

Age-related low skeletal muscle mass correlates with joint space narrowing in knee osteoarthritis in a South Korean population: a cross-sectional, case-control study: Hyun-Je Kim, Young-Hoon Hong; J Yeungnam Med Sci. 2022;39(4):285-293. Published online February 3, 2022; DOI: https://doi.org/10.12701/jyms.2021.01536

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Abstract PDF

Background
This study was conducted to analyze the effects of low skeletal muscle mass index (SMI) and obesity on aging-related osteoarthritis (OA) in the Korean population.
Methods
A total of 16,601 participants who underwent a dual-energy X-ray absorptiometry and 3,976 subjects with knee X-rays according to the modified Kellgren-Lawrence (KL) system were enrolled. Knees of ≥KL grade 2 were classified as radiologic OA. The severity of joint space narrowing (JSN) was classified by X-rays as normal, mild-to-moderate, and severe JSN in radiologic OA. The subjects were grouped as normal SMI (SMI of ≥–1 standard deviation [SD] of the mean), low SMI class I (SMI of ≥–2 SDs and <–1 SD), and low SMI class II (SMI of <–2 SDs). Obesity was defined as a body mass index (BMI) of ≥27.5 kg/m2.
Results
The modified KL grade and JSN severity were negatively correlated with the SMI and positively correlated with BMI and age. The SMI was negatively correlated with age. JSN severity was significantly associated with a low SMI class compared to a normal SMI, which was more prominent in low SMI class II than class I. Obesity was significantly associated with more severe JSN, only for obesity with a low SMI class. Furthermore, patients with a low SMI class, regardless of obesity, were prone to having more severe JSN.
Conclusion
This study suggested that a low SMI class was associated with aging and that an age-related low SMI was more critically related to the severity of JSN in OA.

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Causal relationship between sarcopenia and osteoarthritis: a bi-directional two-sample mendelian randomized study
Jiyong Yang, Peng Liu, Shuai Wang, Tao Jiang, Yilong Zhang, Wengang Liu
European Journal of Medical Research.2023;[Epub] CrossRef

Case report

Septic arthritis of the hip joint caused by Klebsiella pneumoniae: a case report: Jeong-Bo Moon, Jun-Hwan Lee, Byung-Ju Ryu; J Yeungnam Med Sci. 2023;40(2):193-197. Published online January 13, 2022; DOI: https://doi.org/10.12701/yujm.2021.01613

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Abstract PDF: Klebsiella pneumoniae is an uncommon cause of septic arthritis in adults. However, late detection can cause serious complications, including joint destruction and immobility. The purpose of this study was to report a case of successfully treated septic arthritis of the hip joint (SAHJ) caused by K. pneumoniae. A 49-year-old female patient presented to our hospital with fever and progressive severe pain in the right hip area. Although there was no abnormality on plain radiographs, ultrasonography revealed diffuse swelling of the right hip joint. Under ultrasonography guidance, the hip joint fluid was aspirated, and Gram staining and culturing were performed. The patient’s pain was significantly reduced after the joint aspiration. The Gram staining and culturing revealed gram-negative bacilli, which were subsequently identified as K. pneumoniae. According to the results, systemic intravenous antibiotic (ceftriaxone) was administered without complications, and the patient was discharged on oral antibiotic (ciprofloxacin). Clinical cases of septic arthritis of the knee or sacroiliac joint have been occasionally reported in adults, but cases of SAHJ are rare. Moreover, K. pneumonia-induced SAHJ has not been reported to date. Therefore, we report this very rare case and its successful treatment.

Review article

Current perspectives in stem cell therapies for osteoarthritis of the knee: Gi Beom Kim, Oog-Jin Shon; Yeungnam Univ J Med. 2020;37(3):149-158. Published online April 13, 2020; DOI: https://doi.org/10.12701/yujm.2020.00157

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Abstract PDF

Mesenchymal stem cells (MSCs) are emerging as an attractive option for osteoarthritis (OA) of the knee joint, due to their marked disease-modifying ability and chondrogenic potential. MSCs can be isolated from various organ tissues, such as bone marrow, adipose tissue, synovium, umbilical cord blood, and articular cartilage with similar phenotypic characteristics but different proliferation and differentiation potentials. They can be differentiated into a variety of connective tissues such as bone, adipose tissue, cartilage, intervertebral discs, ligaments, and muscles. Although several studies have reported on the clinical efficacy of MSCs in knee OA, the results lack consistency. Furthermore, there is no consensus regarding the proper cell dosage and application method to achieve the optimal effect of stem cells. Therefore, the purpose of this study is to review the characteristics of various type of stem cells in knee OA, especially MSCs. Moreover, we summarize the clinical issues faced during the application of MSCs.

Citations

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Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis
Christopher J. Rogers, Robert Harman, Mitchell B. Sheinkop, Peter Hanson, Mary A. Ambach, Tal David, Rahul Desai, Steven Sampson, Danielle Aufierro, Jay Bowen, Gerard Malanga
Stem Cells and Development.2024; 33(7-8): 168. CrossRef
Safety and Efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis: a Phase I/IIa randomised controlled trial.
Julien Freitag, Matthew Chamberlain, James Wickham, Kiran Shah, Flavia Cicuttini, Yuanyuan Wang, Ann Solterbeck
Osteoarthritis and Cartilage Open.2024; : 100500. CrossRef
Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review
Pengwei Zhang, Bo Dong, Puwei Yuan, Xun Li
Journal of Orthopaedic Surgery and Research.2023;[Epub] CrossRef
Scaffold-Free Cartilage Construct from Infrapatellar Fat Pad Stem Cells for Cartilage Restoration
Orada Sriwatananukulkit, Tulyapruek Tawonsawatruk, Kasem Rattanapinyopituk, Ticomporn Luangwattanawilai, Narongrit Srikaew, Ruedee Hemstapat
Tissue Engineering Part A.2022; 28(5-6): 199. CrossRef
Autologous Protein Solution Effect on Chondrogenic Differentiation of Mesenchymal Stem Cells from Adipose Tissue and Bone Marrow in an Osteoarthritic Environment
Stefania Pagani, Francesca Veronesi, Gianluca Giavaresi, Giuseppe Filardo, Tiziana Papio, Iacopo Romandini, Milena Fini
CARTILAGE.2021; 13(2_suppl): 225S. CrossRef
Mesenchymal Stem Cell-Derived Exosomes and Their Therapeutic Potential for Osteoarthritis
Gi Beom Kim, Oog-Jin Shon, Min-Soo Seo, Young Choi, Wook Tae Park, Gun Woo Lee
Biology.2021; 10(4): 285. CrossRef
Molecular basis for new approaches to therapy of osteoarthritis (part I)
E. V. Chetina, G. A. Markova, A. M. Lila
Modern Rheumatology Journal.2021; 15(4): 7. CrossRef
The therapeutic potential of mesenchymal stem cells in treating osteoporosis
Tianning Chen, Tieyi Yang, Weiwei Zhang, Jin Shao
Biological Research.2021;[Epub] CrossRef
The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease
Robert A. Culibrk, Mariah S. Hahn
Frontiers in Aging Neuroscience.2020;[Epub] CrossRef

Case Reports

Rheumatoid arthritis accompanied by Gitelman syndrome: Min Gi Park, Ji Hyun Lee, Sung Jun Kim, Su Ho Park, Suk Ki Park, Joon Sul Choi, Ji Yeon Hwang; Yeungnam Univ J Med. 2017;34(1):101-105. Published online June 30, 2017; DOI: https://doi.org/10.12701/yujm.2017.34.1.101

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Abstract PDF: Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.

Subcutaneous tissue calcification in a patient with rheumatoid arthritis.: Dong Hyun Kim, Kyung Jin Kim, Sung Min Kwon, Sung Ouk Cha, Jung Ouk Lee; Yeungnam Univ J Med. 2016;33(2):120-124. Published online December 31, 2016; DOI: https://doi.org/10.12701/yujm.2016.33.2.120

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Abstract PDF: Subcutaneous tissue calcification in rheumatic diseases usually occurs in connective tissue diseases, such as systemic lupus erythematosus, scleroderma, and dermatomyositis. Domestic cases of calcification in rheumatoid arthritis have not been reported. The mechanism of subcutaneous tissue calcification may differ depending on the cause and it can develop on all parts of the body. Calcification occurring in rheumatic diseases is a major mechanism of tissue damage caused by chronic inflammation. No standard therapy for calcification has been established; however, many studies have reported on medical and surgical treatment. We report on subcutaneous tissue calcification in a rheumatoid arthritis patient tissue calcification on both sides of the buttocks, the upper limbs, and the lower limbs.

An overlap syndrome of Churg-Strauss syndrome and rheumatoid arthritis.: Seung Il Bae, Jong Geol Jang, Hun Tae Kim, Hee Yun Ahn, Min Jung Kim, Hyun Je Kim, Choong Ki Lee, Young Hoon Hong; Yeungnam Univ J Med. 2015;32(2):127-131. Published online December 31, 2015; DOI: https://doi.org/10.12701/yujm.2015.32.2.127

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Abstract PDF: Churg-Strauss syndrome (CSS) is a necrotizing vasculitis with extra-, peri-vascular eosinophilic infiltration. Chronic symmetric polyarthritis with the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody are the mainstay of rheumatoid arthritis (RA) diagnosis. Mononeuritis multiplex is a peripheral neuropathy involving more than 2 separate nerve areas. A 62-year-old male patient was referred for left foot drop and polyarthritis of both hands and feet for 4 months. During evaluation, mononeuritis multiplex was detected on nerve conduction study and electromyography tests: vasculitis with neutrophil, eosinophil, and lymphocyte infiltration on peroneal nerve biopsy. A positive response to methacholin and bronchodilator was observed on the pulmonary function test. Radiologic tests showed peri-articular soft tissue swelling and osteopenia on both hand and foot. Marked peripheral eosinophilia, high RF, and positive perinuclear anti-neutrophil cytoplasmic antibody were detected on blood tests. Here, we report on a patient with overlap syndrome of CSS and RA with review of the relevant literature, from which a few references to overlap syndrome of CSS and RA were available.

Two Cases of Severe Pancytopenia Associated with Low-Dose Methotrexate Therapy in Patients with Chronic Kidney Disease and Rheumatoid Arthritis.: Hong Ik Kim, Woo Hyun Lee, Jang Seok Oh, Hyo Rim Hong, In Hee Lee; Yeungnam Univ J Med. 2011;28(1):60-69. Published online June 30, 2011; DOI: https://doi.org/10.12701/yujm.2011.28.1.60

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Abstract PDF: Due to its efficacy and tolerability, low dose oral methotrexate(MTX) therapy has been widely used for treatment of rheumatoid arthritis(RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease(CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240mg) and 4 years(cumulative dose 1,320mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells(RBCs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included RBC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

Review Article

Epidemiology, Risk Factors, and Pathophysiology of Osteoarthritis: Choong-ki Lee; Yeungnam Univ J Med. 2007;24(2 Suppl):S132-141. Published online December 31, 2007; DOI: https://doi.org/10.12701/yujm.2007.24.2S.S132

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Abstract PDF

Osteoarthritis (OA) is the most prevalent form of arthritis and a major cause of disability in people aged 65 and older. OA is not a single disease; rather, it is a group of overlapping yet distinct diseases with different etiologies but similar pathologic, morphologic, and clinical outcomes. OA occurs when the dynammic equilibrium between the breakdown and reapir of joint tissues is overwhelmed. Systemic and local biomechanical factors contribute to the development of the disease, with systemic factors also making the joint vulnerable and resulting in a greater impact of local joint factors. Systemic risk factors include ethnicity, gender, age, genetic factors, hormonal status, bone density, and nutritional factors. Local biomechanical factors include altered joint biomechanics, prior injuries, the effects of physical activities, sports participation, occupation, developmental abnormalities, and obesity. The normal joint is protected by biomechanical factors such as alignment and muscle strength, the lubrication provided by the synovial fluid, and the shock-absorbing function of bone and cartilage. When these functions are altered, changes occur at both the macroscopic and cellular levels, with derangements in any structure contributing to further joint destruction. 1) Further studies of both risk factor modification and cellular changes in OA will hopefully continue to enhance our understanding of this complex disease and lead to improved outcomes.

Citations

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Prevalence of Osteoarthritis and Its Affecting Factors among a Korean Population Aged 50 and Over
Hye-Ryoung Kim, Eun-Jung Kim
Journal of Korean Public Health Nursing.2013; 27(1): 27. CrossRef

Review

Identification of Interleukin 1-Responsive Genes in Human Chondrosarcoma SW1354 cells by cDNA Microarray Technology.: Jun Ha Jeon, Yong Wook Jung, Dae Young Yun, Hyun Do Kim, Chang Mo Kwon, Young Hoon Hong, Jae Ryong Kim, Choong Ki Lee; Yeungnam Univ J Med. 2007;24(1):24-40. Published online June 30, 2007; DOI: https://doi.org/10.12701/yujm.2007.24.1.24

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Abstract PDF: BACKGROUND
Accumulating evidence shows that interleukin(IL)-1 plays a critical role in inflammation and connective tissue destruction observed in both osteoarthritis and rheumatoid arthritis. IL-1 induces gene expression related to cytokines, chemokines and matrix metalloproteinases by activation of many different transcription factors. MATERIALS AND METHODS: The chondrosarcoma cell line, SW1353, is known to be a valuable in vitro system for investigating catabolic gene regulation by IL-1beta in chondrocytic cells. To explore and analyze the changes in gene expression by IL-1 responsible for arthritis, SW1353 was treated with IL-1 for 1, 6 and 24 h and then total RNAs were purified for each time. The changes in gene expression were analyzed with 17k human cDNA microarrays and validated by semi-quantitative RT-PCR. RESULTS: Greater than a two-fold change was observed in 1,200 genes including metallothioneins, matrix metalloproteinases, extracellular matrix proteins, antioxidant proteins, cytoskeleton proteins, cell cycle regulatory proteins, proteins for cell growth and apoptosis, signaling proteins and transcription factors. These changes appeared to be correlate with the pathophysiological changes observed in early osteoarthritis. CONCLUSION: cDNA microarray analysis revealed a marked variability in gene expression, and provided insight into the overall molecular changes. The result of this study provide initial information for further studies to identify therapeutic targets in osteoarthritis pathogenesis.

Case Report

A Case of Pyoderma Gangrenosum in Rheumotoid Arthritis Patient.: Dong Hwan Ryu, Chang Mo Kwon, Jung Hun Lee, Young Hun Hong, Choong Ki Lee; Yeungnam Univ J Med. 2003;20(1):79-84. Published online June 30, 2003; DOI: https://doi.org/10.12701/yujm.2003.20.1.79

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Abstract PDF: Pyoderma gangrenosum is uncommon neutrophilic dermatosis characterized by richness of the mature neutrophilic polynuclear dermal infiltrate. Pyoderma gangrenosum is associated with variable diseases, most commonly inflammatory bowel disease, hematological diseases, malignancies, but it is reported rarely in rheumatoid arthritis. We report a case of pyoderma gangrenosum in rheumoid arthritis patient. A 50-year-old woman admitted to our hospital due to painful pretibial ulcerative skin lesions. She had been treated as rheumatoid arthritis for 8 years. At admission, body temperature was 36.5degrees C and other vital sign was unremarkable. Physical examination revealed right pretibial ulceration, multiple pustules on left pretibial area and both palms. Laboratory studies revealed WBC count 7,600/uL (neutrophils 60.3%, eosinophil 3.2%), hemoglobin 11.4 g/dL, platelet count 319,000/uL, ESR 65 mm/hour. Other lab findings were also unremarkable. Skin biopsy was done, which showed dense dermal infiltrate of neutrophils and wound culture were negative. By 8 weeks after systemic high dose corticosteroid (1 mg/kg/day), cyclosporine A (5 mg/kg/day), sulfasalazine 2 g therapy, symptoms and skin ulceration were being improved. Without skin relapse, she is followed up our hospital with low dose corticosteroid and sulfasalazine.

Original Article

The Effect of Long Chain N-3 Polyunsaturated Fatty Acids on Development of Collagen-induced Arthritis in Rats.: Kyung Ho Shin, Se Dong Kim, Hwan Jin Jeon, Eung Chan Jang, Suck Kang Lee; Yeungnam Univ J Med. 2002;19(1):39-48. Published online June 30, 2002; DOI: https://doi.org/10.12701/yujm.2002.19.1.39

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Abstract PDF: BACKGROUND
The treatment of rheumatoid arthritis still depend on conserve therapy in major. Recent studies report that n-3 polyunsaturated fatty acids(PUFA) could modulate the incidence and progress of arthritis. The purpose of this study was to investigate the effects of n-3 PUFA on the development of collagen-induced arthritis in rats. MATERIALS AND METHODS: Female Louvain rats were used for this experiment. Rats were randomly assigned into either normal(n=8) or collagen-immunized groups, and collagen immunized groups were divided into control(n=8, normal diet) and n-3 PUFA(n=8, 5% n-3 PUFA in diet) groups. One week after feeding n-3 PUFA to rats, they were immunized with type II collagen emulsified in incomplete Freund's adjuvant into tail and back. Development of arthritis was confirmed by x-ray and microscopic examination. RESULTS: Incidence of arthritis at the 5th week after immunization was 38% in control and 0% in n-3 PUFA. Rats with arthritis showed edema in hind paws and inflammation in synovial membrane of the knee joint. Plasma glucose and insulin were not changed by both of immunization and diet. Plasma triglycerides and cholesterol concentrations were decreased by n-3 PUFA. CONCLUSION: n-3 PUFA may prevent or treat collagen-induced arthritis in rats. Further studies are needed for action mechanism of it.

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