Dataset Information

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

ABSTRACT: OBJECTIVE:The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN:141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS:Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS:This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

SUBMITTER: Joseph GB

PROVIDER: S-EPMC6050081 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

Joseph G B GB Nevitt M C MC McCulloch C E CE Neumann J J Lynch J A JA Heilmeier U U Lane N E NE Link T M TM

Osteoarthritis and cartilage 20180523 8

<h4>Objective</h4>The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI).<h4>Design</h4>141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic re ...[more]

PMID: 29802973

Similar Datasets

Project description:Objectives:The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods:The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results:In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1?-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion:This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients.Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:288-301. DOI: 10.1302/2046-3758.86.BJR-2018-0297.R1.

Project description:ObjectivesThe aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).MethodsThe expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo.ResultsIn total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues.ConclusionThis study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients.Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290-303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1.

Project description:BACKGROUND:Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation. METHODS:Baseline data of two randomised clinical trials (NCT00486434 and NCT00704847) in patients with radiographic OA and presence of pain were analysed post hoc. A subgroup with available urine samples and evaluable radiographs for both knees (N = 1241) was analysed. Urine CTX-I, urine CTX-II and serum osteocalcin were analysed for associations with combined Kellgren-Lawrence (KL) scores, gender and pain for both knees to assess the contribution of joints at different stages. RESULTS:Pain, BMI, age, gender and KL grade were all significantly associated with uCTX-II. The association between pain and CTX-II appeared to be driven by weight-bearing pain. The level of uCTX-II incrementally increased with higher radiographic severity of each knee. Levels of bone markers CTX-I and osteocalcin were both significantly associated with BMI and gender, but neither were associated with radiographic severity. Biomarker levels between male or female groups of identical KL scores were found to be higher in females compared to males in some but not all KL score groups. CONCLUSIONS:These results indicate that levels of uCTX-II are independently associated with radiographic severity of OA and pain intensity. CTX-II was associated with weight-bearing pain, but not non-weight-bearing pain, independent of co-variates. Bilateral OA knee joints appear to contribute to uCTX-II levels in an incremental manner according to radiographic severity of single joints. The data suggest that biomarker differences between genders should be taken into account when evaluating these markers in the context of structural features of OA.

Project description:ObjectivesTo develop an MR-based semi-quantitative meniscus scoring technique for postoperative assessment of the degree of meniscal resection, to test its reproducibility, and to study the relationship between the amount of resection and degenerative disease burden.MethodsWe studied the right knee of 135 participants from the Osteoarthritis Initiative that underwent meniscal surgery an average of 14 years previously. The amount of meniscal resection was assessed on baseline 3.0-T MRIs and calculated as meniscus resection score (MenRS) with a range of 0 to 18. Knee abnormalities at baseline and 48 months were graded using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Subjects were also stratified according to meniscal resection performed after injury versus without preceding injury. Statistical analysis included intra-class correlation coefficient (ICC) to determine reproducibility as well as regression models and partial correlations to correlate MenRS with WORMS outcomes.ResultsICC values for intra- and inter-observer reproducibility of MenRS were 0.980 and 0.977, respectively. Overall, the amount of meniscal resection showed a significant correlation with baseline WORMS grades: higher MenRS was associated with higher total WORMS grades (p = 0.004) and cartilage (p = 0.004) and ligament (p < 0.001) subscores. However, no significant association between MenRS and change in WORMS grades over 48 months was found. The relationship between MenRS and baseline WORMS grades did not change after adjusting for a reported history of knee injury.ConclusionsPostoperative assessment of the knee following partial meniscectomy using the newly developed MenRS showed excellent reproducibility and significant cross-sectional correlation with WORMS gradings.Key points• The newly developed semi-quantitative MR-based meniscal resection score demonstrated excellent reproducibility. • A significant correlation between the amount of meniscal resection measured using the newly developed score and the degree of overall knee joint degenerative disease and cartilage defects was found.

Dataset Information

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

Publications

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets