Proteomic data of osteoarthritis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Lin Xue
PROVIDER: PXD051627 | iProX | Fri Apr 19 00:00:00 BST 2024
REPOSITORIES: iProX
Similar Datasets
Project description:To date, all of the prior osteoarthritic microarray studies in human tissue have focused on the overlying articular cartilage, meniscus, or synovium but not the underlying subchondral bone. In our previous study, our group developed a methodology for high quality RNA isolation from site-matched cartilage and bone from human knee joints, which allowed us to perform candidate gene expression analysis on the subchohndral bone (published on Osteoarthritis and Cartilage on Dec/5/2012 (doi: 10.1016/j.joca.2012.11.016). To the best of our knowledge, the current study is the first to successfully perform whole-genome microarray profiling analyses of human osteoarthritic subchondral bone. We believe our comprehensive microarray results can improve the understanding of the pathogenesis of osteoarthritis and could further contribute to the development of new biomarker and therapeutic strategies in osteoarthritis. Following histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by microcomputed tomography, we isolated total RNA from regions of interest from human OA (n=20) and non-OA (n=5) knee lateral and medial tibial plateaus (LT and MT). A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from nine OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples.
2013-10-24 | E-GEOD-51588 | biostudies-arrayexpress
Project description:Introduction: Emerging evidence suggests long non-coding RNA (lncRNA) H19 is associated with osteoarthritis (OA) pathology. However, how H19 contributes to OA has not been reported. This study aims to investigate the biological function of H19 in OA subchondral bone remodeling and OA progression. Methods: Clinical joint samples and OA animal models induced by medial meniscus destabilization (DMM) surgery were used to verify the causal relationship between osteocyte H19 and OA subchondral bone and cartilage changes. MLO-Y4 osteocyte cells subjected to fluid shear stress were used to verify the mechanism underlying H19-mediated mechano-response. Finally, the antisense oligonucleotide (ASO) against H19 was delivered to mice knee joints by magnetic metal-organic framework (MMOF) nanoparticles in order to develop a site-specific delivery method for targeting osteocyte H19 for OA treatment. Results: Both clinical OA subchondral bone and wildtype mice with DMM-induced OA exhibit aberrant higher subchondral bone mass with more H19 expressing osteocytes. On the contrary, osteocyte-specific deletion of H19 mice is less vulnerable to DMM-induced OA phenotype. In MLO-Y4 cells, H19-mediated osteocyte mechano-response through PI3K/AKT/GSK3 signals activation by EZH2-induced H3K27me3 regulation on PP2A inhibition. Targeted inhibition of H19 (using ASO-loaded MMOF) substantially alleviates subchondral bone remodeling and OA phenotype. Discussion: In summary, our results provide new evidence that the elevated H19 expression in osteocytes may contribute to aberrant subchondral bone remodeling and OA progression. H19 appears to be required for the osteocyte response to mechanical stimulation, and targeting H19 represents a new promising approach for OA treatment.
2025-03-05 | GSE254053 | GEO
Project description:To date, all of the prior osteoarthritic microarray studies in human tissue have focused on the overlying articular cartilage, meniscus, or synovium but not the underlying subchondral bone. In our previous study, our group developed a methodology for high quality RNA isolation from site-matched cartilage and bone from human knee joints, which allowed us to perform candidate gene expression analysis on the subchohndral bone (published on Osteoarthritis and Cartilage on Dec/5/2012 (doi: 10.1016/j.joca.2012.11.016). To the best of our knowledge, the current study is the first to successfully perform whole-genome microarray profiling analyses of human osteoarthritic subchondral bone. We believe our comprehensive microarray results can improve the understanding of the pathogenesis of osteoarthritis and could further contribute to the development of new biomarker and therapeutic strategies in osteoarthritis.
2013-10-24 | GSE51588 | GEO
Project description:Osteoarthritis (OA) is the most common joint disease and this is a major cause of joint pain and disability in the aging population. Its etiology is multifactorial (i.e., age, obesity, joint injury, genetic predisposition), and the pathophysiologic process affects the entirety of the joint (Martel-Pelletier J et al. Osteoarthritis. Nature reviews Disease primers. 2016;2:16072). Although it is not yet clear if it precedes or occurs subsequently to cartilage damage, subchondral bone sclerosis is an important feature in OA pathophysiology (Goldring SR et al. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat Rev Rheumatol. 2016;12:632-44). It is characterized by local bone resorption and the accumulation of weakly mineralized osteoid substance (Bailey AJ et al. Phenotypic expression of osteoblast collagen in osteoarthritic bone: production of type I homotrimer. Int J Biochem Cell Biol. 2002;34:176-82). Subchondral bone sclerosis is suspected to be linked to cartilage degradation, not only by modifying the mechanical stresses transmitted to the cartilage, but also by releasing biochemical factors with an activity on cartilage metabolism (Sanchez C et al. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthritis Cartilage. 2005;13:979-87; Sanchez C et al. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2005;13:988-97; Westacott CI et al J. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum. 1997;40:1282-91. We have previously demonstrated that osteoblasts isolated from subchondral OA bone exhibited an altered phenotype. More precisely, we showed that osteoblasts coming from the thickening (called sclerotic, SC) of subchondral bone located just below a cartilage lesion produced higher levels of alkaline phosphatase, interleukin (IL)-6, IL-8, prostaglandinE2, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-9 and transforming growth factor(TGF)-β1 and type I collagen than osteoblasts coming from the non-thickening neighboring area (called non-sclerotic area, NSC) (Sanchez C et al. Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone. Arthritis Rheum. 2008;58:442-55; Sanchez C et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression. Arthritis Rheum. 2012;64:1193-203.) To compare secretome of cells living in different in vivo conditions is useful, not only to better understand the pathological mechanisms underlying changes in OA subchondral bone, but also to identify soluble biomarkers potentially reflecting these changes. Using our well-characterised human subchondral osteoblast culture model, we compared the secretome of osteoblasts coming from sclerotic and non sclerotic OA subchondral bone. This approach allowed to identify changes in secretome that contribute to explain some subchondral bone abnormalities in OA and to propose osteomodulin and fibulin-3 as potential biomarkers of OA subchondral bone remodelling.
2018-03-20 | PXD008494 | Pride
Project description:Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and alterations in subchondral bone, ultimately leading to chronic pain and impaired mobility. This study aimed to identify plasma proteomic alterations in OA patients before and after arthroplasty in order to reveal biomarkers associated with both ongoing disease processes and postoperative recovery.
The study cohort consisted of eighteen individuals: eight OA patients undergoing total knee or hip arthroplasty and ten healthy controls matched for age, sex, and body mass index. Plasma samples were depleted of high-abundance proteins, enzymatically digested, and subsequently analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to characterize proteomic changes.
2026-03-30 | PXD075088 | JPOST Repository
Project description:The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 (SMAD3) and Wnt family member 5A (WNT5A) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA. Additionally, 26 dysregulated genes with potential miRNA⁻mRNA interactions were identified in OA knee chondrocytes. Myristoylated alanine rich protein kinase C substrate (MARCKS), epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in Gene Expression Omnibus database. The Ingenuity Pathway Analysis identified MARCKS to be associated with the outgrowth of neurite, and novel miRNA regulations were proposed to play critical roles in the pathogenesis of the altered OA knee joint microenvironment. The current findings suggest new perspectives in studying novel genes potentially contributing to arthritic joint pain in knee OA, which may assist in finding new targets for OA treatment.
2018-12-18 | GSE110606 | GEO
Project description:Aberrant subchondral bone remodeling is a critical factor in osteoarthritis (OA) pathogenesis. We observed significant downregulation of Mitogen-induced gene-6 (Mig6) and upregulation of EGFR phosphorylation in subchondral bone osteoblasts, strongly correlating with OA severity in human and animal models. Mig6 is the most important factor mediating mechanical stress-activated EGFR, which inhibits osteogenic activity and modulates mechano-responsiveness. Osteoblast-specific Mig6 deletion exacerbated OA progression by promoting subchondral bone remodeling, whereas gefitinib-mediated inhibition of EGFR phosphorylation attenuated OA symptoms in mice, rats, and Mig6 knockout rats. Furthermore, loss of osteoblastic Mig6 disrupted the subchondral bone microenvironment, increasing inflammation, angiogenesis, and neuronal activity. Mechanistically, aberrant mechanical loading downregulated Mig6, activating phosphorylation of EGFR and the downstream JAK-STAT3 pathway, thereby promoting subchondral bone remodeling and accelerating OA progression. These findings reveal a novel mechanism by which osteoblastic Mig6 regulates subchondral bone remodeling in OA, highlighting Mig6 as a potential therapeutic target.
2025-07-31 | GSE302025 | GEO
Project description:With an increasing number of affected individuals and a trend towards younger age of onset, research on the treatment of knee osteoarthritis (KOA) is facing significant challenges. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, and pathological remodeling of subchondral bone may be one of the key factors mediating the degeneration of the overlying cartilage. This study constructed a postmenopausal KOA mice model in bipedal mice to better understand how subchondral bone remodeling and cartilage degeneration interact during KOA development. The femoral condyle tissue, excluding the growth plate, was isolated from the distal epiphyseal line in KOA mice for single cell RNA sequencing and analysis. And a single-cell atlas of the osteochondral composite tissue, including chondrocytes, endothelia cells, osteoblasts, progenitor cells, and so on, was successfully constructed. Furthermore, three novel subtypes of chondrocytes, including Smoc2+ angiogenic chondrocytes, Angptl7+ angiogenic chondrocytes, and Col1a1+ osteogenic chondrocytes, were identified. Angptl7+ chondrocytes activated endothelia cells via the Fgf2-Fgfr2 interaction pathway, and promoted angiogenesis and vascular invasion in subchondral bone of KOA mice. The quantity of H-type vessels, which recruit numerous osterix+ osteoprogenitor cells and stimulate osteogenesis, exhibited an increase within the subchondral bone of mice with KOA. While Sparc+ osteoblast negatively regulated the bone mineralization and osteoblastic differentiation, aggravated the pathological remodeling of subchondral bone and KOA progression. These findings suggest that there are new avenues for potential therapeutic interventions in the treatment of KOA.
2025-02-12 | GSE267616 | GEO
Project description:Osteoarthritis (OA) of the knee is a degenerative condition of the skeletal extracellular matrix (ECM) marked by the loss of articular cartilage and subchondral bone homeostasis that preferentially occurs in the medial side of the joint. Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers for disease progression. MALDI-Mass Spectrometry Imaging (MSI) allows molecular spatial mapping that is used to investigate the proteomic landscape of OA providing molecular details on the progression of joint degeneration. Entire histologic sections of human tibial plateaus from OA patients and cadaveric controls were treated with collagenase III to target ECM proteins prior to imaging using a timsTOF flex mass spectrometer (Bruker) for the first reported study of MALDI-MSI on bone protein. Data from healthy cadaveric joints and both lateral and medial sides of OA joints were automatically segmented identifying distinct areas of joint damage. Candidate ECM markers comparing either OA to cadaveric tissues or OA medial to OA lateral tissues resulted in 44 candidate peptides that emphasize the significant spatial difference between OA and healthy bone (AUROC >0.85). 31 of 44 peptide markers, resulting from ECM proteins such as COL1A1, COL3A1, and novel detection of COL6A1 and COL6A3 in bone, with significantly elevated abundance in our full OA cohort, indicate disease progression. Spatial maps of these markers revealed distinct tissue damage and disease pathologies in the subchondral bone that are related to protein structural changes in the ECM, changes that may precede overlying cartilage loss in OA.
2024-04-01 | MSV000094448 | MassIVE
Project description:The composition of subchondral bone cell types in patients with osteoarthritis (OA) and the underlying spatiotemporal transformation processes remain unknown. Here, we identified various subchondral bone cell subsets and investigated the mechanism of subchondral bone microstructure alteration using single-cell RNA sequencing (scRNA-seq).
2022-09-20 | GSE196678 | GEO