Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis

Rajandran, Sureka Naidu; Ann, Cheryl; Tan, Jerry; Liu, Jin; Sl, Wong; Leung, Ying Ying

doi:10.3389/fmed.2020.554669

Cited by 16 publications

(19 citation statements)

References 44 publications

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“…The biomarkers’ detection in the biological fluids was further examined over time and compared with the findings of previous reports [ 49 , 50 , 51 , 52 , 53 ]. In contrast to the previous report [ 54 , 55 ], the proinflammatory markers were under the detection limit in all groups. This may be attributed to the single-joint combinational ACLT+MMx model, which could not develop meaningful systemic inflammation.…”

Section: Discussioncontrasting

confidence: 99%

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Huang

Yang

Busa

et al. 2021

IJMS

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Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage’s integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.

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Section: Discussioncontrasting

confidence: 99%

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Huang

Yang

Busa

et al. 2021

IJMS

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“…The knee joint has been subjected to extensive orthopedic research over the last century, mainly due to its complex anatomical structure and the fact that it is commonly affected in a variety of orthopedic diseases (1)(2)(3). The macroscopic anatomy and clinical significance of the tibial plateau, intercondylar fossa (ICF), and anterior and posterior cruciate ligaments (ACL & PCL) have been well-established (3)(4)(5). In recent years, the discovery of new knee joint-related anatomical structures has been rare (6).…”

Section: Introductionmentioning

confidence: 99%

Discovery of Lijianmin-Chengkun Complexes and Their Oncological Application in Osseous and Intraarticular Lesions Around the Knee

Shao

Zhang

et al. 2021

Front. Surg.

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Objective: This research aims to refresh the limited understanding about the canal and vascular structures within the epiphysis and metaphysis of the tibia and femur and their oncological significance.Methods: This study was started with characterization of a novel structure using radiographs and anatomic dissections, followed by a descriptive clinical study with 55 participants to investigate the effects of tumors on this novel discovery and a retrospective cohort study with 82 participants to investigate whether the structure would be a risk factor for tumor recurrence after the curettage of giant cell tumor of bone.Results: A new anatomical knee structure, the Lijianmin-Chengkun (LC) complex, was discovered in healthy adults, and its clinical implications were examined in this study. This new-found anatomical structure is composed of an epiphyseal and metaphyseal canal which surrounds a blood vessel, foramen, and foramen-covered synovium. All LC complexes showed similar radiographical, anatomical, and histological characteristics and were located within specific tibial and femoral intercondylar regions. These LC complexes seem to facilitate tumor residue and extension and may be a risk factor for tumor recurrence after curettage of femoral and tibial giant cell tumors (P = 0.031).Conclusion: The LC complexes are related to local tumor recurrence and bidirectional tumor dissemination between intraosseous and intraarticular regions. These findings have opened up a new perspective and may provide new targets for intervention in malignant and aggressive tumors around the knee joint.

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“…It is reported that interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), fibroblast growth factor (FGF-2), and transforming growth factor beta 1 (TGFβ-1) showed a predominant increase in protein levels, while activin A mainly decreased in the synovial fluid of OA patients during knee joint distraction (Watt et al, 2020;Henrotin, 2022). Interestingly, in a study of knee OA, researchers found that serum lipopolysaccharide-binding protein (LBP), IL-6, interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and the cluster of differentiation 14 (CD14) of synovial fluid were associated with most MRI features in an earlier stage of knee OA (Rajandran et al, 2020). Batshon et al (2020) found that the NT/CT deacetylase sirtuin-1 (SIRT1) ratio correlated with OA in both mice and humans, and this increase was mainly due to NT fragment level increase from non-senescent chondrocyte apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

et al. 2022

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Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with p-value<0.05 and | log2FC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein–protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.

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Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis

Cited by 16 publications

References 44 publications

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Discovery of Lijianmin-Chengkun Complexes and Their Oncological Application in Osseous and Intraarticular Lesions Around the Knee

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

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