Background: Connective tissue growth factor (CTGF)-induced angiogenesis is a crucial factor in rheumatoid arthritis (RA), but CTGF-interacting protein and related molecular mechanism of their interaction have not been fully elucidated.
Methods: CTGF-interacting proteins were identified through the LC-MS/MS analysis of the Co-IP products from fibroblast-like synoviocyte (FLS) lysates, and the interaction between CTGF and annexin A2 (ANXA2) was further confirmed through Co-IP and BiFC assay. The binding domain, mutant, mechanism, and angiogenesis function were assessed by homology modeling, molecular docking, MTT, cell scratch, tube formation, and chick chorioallantoic membrane (CAM) assays. Additionally, severe combined immunodeficiency (SCID) mouse co-implantation model was constructed to confirm the effect of ANXA2/CTGF-TSP1 in the process of RA in vivo.
Results: ANXA2 was identified and verified as an interaction partner of CTGF for the first time by Co-IP and LC-MS/MS analysis. Co-localization of CTGF and ANXA2 was observed in RA-FLS, and direct interaction of the TSP-1 domain of CTGF and ANXA2 was determined in HEK293T cells. The spatial conformation and stable combination of the ANXA2/CTGF-TSP1 complex were assessed by homology modeling in the biomimetic environment. The function of the ANXA2/CTGF-TSP1 complex was proved on promoting FLS proliferation, migration, and angiogenesis in vitro and deteriorating FLS invasion and joint damage in SCID mice.
Conclusions: TSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547044 | PMC |
| http://dx.doi.org/10.1186/s13075-021-02656-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantification of Citrullinated Histone H3 as a Marker for Neutrophil Extracellular Traps Correlated to Clinical Characteristics of Patients with Systemic Lupus Erythematosus.
Arch Immunol Ther Exp (Warsz)
January 2025
Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis is not fully understood to date. One of the suggested mechanisms for its development is NETosis, which involves the release of a specific network consisting of chromatin, proteins, and enzymes from neutrophils, stimulating the immune system. One of its markers is citrullinated histone H3 (H3Cit).
View Article and Find Full Text PDFStudy of distribution and morphological characteristics of the trabecular bone in the uncinate process of the cervical spine using micro-computed tomography.
PLoS One
January 2025
Human Anatomy Teaching and Research Section (Digital Medical Center), Inner Mongolia Medical University Basic Medical College, Hohhot, China.
The cervical uncinate process is a unique structure of the cervical spine that undergoes significant changes in its morphological characteristics with age, and these changes may be related to osteoporosis. This study aimed to observe the distribution of cancellous bone in the cervical uncinate process and its morphological features using micro-computed tomography (Micro-CT) to gain a deeper understanding of the morphological characteristics of the uncinate microstructure. We performed Micro-CT scans on 31 sets of C3-C7 vertebrae, a total of 155 intact bone samples, and subsequently used the measurement software with the Micro-CT system to obtain parameters related to the cancellous bone of the uncinate process.
View Article and Find Full Text PDFCD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
PLoS One
January 2025
Lawrence Livermore National Laboratory, Physical and Life Science Directorate, Livermore, CA, United States of America.
Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve.
View Article and Find Full Text PDFMARCHF8-mediated ubiquitination via TGFBI regulates NF-κB dependent inflammatory responses and ECM degradation in intervertebral disc degeneration.
PLoS One
January 2025
Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, China.
Aim: To explore the role of the hub gene Transforming Growth Factor Beta Induced (TGFBI) in Intervertebral disc degeneration (IDD) pathogenesis and its regulatory relationship with Membrane Associated Ring-CH-Type Finger 8 (MARCHF8).
Background: IDD is a prevalent musculoskeletal disorder leading to spinal pathology. Despite its ubiquity and impact, effective therapeutic strategies remain to be explored.
Identification of degenerative precursors at the wrist with advanced imaging: current updates.
J Hand Surg Eur Vol
January 2025
Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
Articular malalignment and ulnocarpal impaction can progress to osteoarthritis in the wrist. This may be triggered by tears of the scapholunate ligament (rarely the lunotriquetral ligament) or the foveal lamina of the triangular fibrocartilage complex. In the pre-degenerative stages, radiographic findings are inconclusive, and symptoms may be absent or discrete.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!