{"title":"在膝关节骨关节炎大鼠模型中评估关节内注射大鼠骨髓间充质干细胞后的血清生物标志物。","authors":"Abdulwahab Noorwali, Fadwa Aljoud, Amani Alghamdi, Noora Sattami, Taghreed Bashah, Abdulsalam Noorwali, Peter Natesan Pushparaj, Kalamegam Gauthaman","doi":"10.1016/j.heliyon.2024.e39940","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.</p><p><strong>Methods: </strong>Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 10<sup>6</sup> cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).</p><p><strong>Results: </strong>rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.</p><p><strong>Conclusions: </strong>Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.</p>","PeriodicalId":12894,"journal":{"name":"Heliyon","volume":"10 21","pages":"e39940"},"PeriodicalIF":3.4000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565378/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis.\",\"authors\":\"Abdulwahab Noorwali, Fadwa Aljoud, Amani Alghamdi, Noora Sattami, Taghreed Bashah, Abdulsalam Noorwali, Peter Natesan Pushparaj, Kalamegam Gauthaman\",\"doi\":\"10.1016/j.heliyon.2024.e39940\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.</p><p><strong>Methods: </strong>Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 10<sup>6</sup> cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).</p><p><strong>Results: </strong>rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.</p><p><strong>Conclusions: </strong>Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.</p>\",\"PeriodicalId\":12894,\"journal\":{\"name\":\"Heliyon\",\"volume\":\"10 21\",\"pages\":\"e39940\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565378/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heliyon\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.heliyon.2024.e39940\",\"RegionNum\":3,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/15 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heliyon","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.heliyon.2024.e39940","RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/15 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景：骨关节炎（OA）是一种以关节疼痛、功能障碍和残疾为特征的常见关节疾病。本研究探讨了关节内注射大鼠骨髓间充质干细胞（rBM-MSCs）对膝关节OA大鼠的治疗效果：将45只雄性Wistar大鼠随机分为三组（A-C），分别接受生理盐水（NS）或rBM-间充质干细胞的关节内注射。正常对照组（A，n = 15）接受 NS，OA 对照组（B，n = 15）接受 NS，OA 治疗组（C，n = 15）接受 rBM-间充质干细胞（0.5 × 106 cells in 25 μL NS）。rBM-间充质干细胞取自雌性Wistar大鼠，并使用流式细胞术对其干细胞进行表征。对正常膝关节和 OA 膝关节切片进行了组织形态学分析。使用ELISA试剂盒分析了血清生物标志物，包括透明质酸（HA）、交联I型胶原蛋白-1的N-十肽（NTX-1）、NGF、降钙素基因相关肽（CGRP）、基质金属蛋白酶-3（MMP-3）、低聚软骨基质蛋白COMP、白细胞介素-6（IL-6）和可溶性IL-6受体（sIL-6R）。结果：rBM-间充质干细胞的CD29和CD90阳性，CD45表面标记阴性。未经治疗的 OA 组 OA 生物标志物明显升高，但经关节内间叶干细胞治疗后降低。与对照组相比，接受间充质干细胞治疗的 OA 组显示出受损软骨的明显修复：结论：软骨损伤会导致炎性细胞因子水平升高，并与软骨降解相关的血清生物标志物增加有关。关节内给予间充质干细胞显示出有益的效果，包括受损软骨的再生和与炎症相关的血清生物标志物水平的降低。
Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis.
Background: Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.
Methods: Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 106 cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).
Results: rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.
Conclusions: Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.
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