Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with and mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 , either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by HO caused a dose-dependent increase in gene and CCN3 protein expression, along with enhanced expression of and mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced promoter activity via . Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of and mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593953 | PMC |
| http://dx.doi.org/10.3390/ijms21207556 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.
Adv Sci (Weinh)
January 2025
Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, No.7 Weiwu Road, Zhengzhou, Henan, 450003, China.
Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression.
View Article and Find Full Text PDFPolydeoxynucleotide-Loaded Visible Light Photo-Crosslinked Gelatin Methacrylate Hydrogel: Approach to Accelerating Cartilage Regeneration.
Gels
January 2025
Department of Polymer Nano Science & Technology and Polymer Materials Fusion Research Center, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si 54896, Jeonbuk, Republic of Korea.
Articular cartilage faces challenges in self-repair due to the lack of blood vessels and limited chondrocyte concentration. Polydeoxyribonucleotide (PDRN) shows promise for promoting chondrocyte growth and cartilage regeneration, but its delivery has been limited to injections. Continuous PDRN delivery is crucial for effective cartilage regeneration.
View Article and Find Full Text PDFExtracellular Vesicles Derived from Human Umbilical Mesenchymal Stem Cells Transfected with miR-7704 Improved Damaged Cartilage and Reduced Matrix Metallopeptidase 13.
Cells
January 2025
Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.
We aimed to explore the therapeutic efficacy of miR-7704-modified extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) for osteoarthritis (OA) treatment. In vitro experiments demonstrated the successful transfection of miR-7704 into HUCMSCs and the isolation of EVs from these cells. In vivo experiments used an OA mouse model to assess the effects of the injection of miR-7704-modified EVs intra-articularly.
View Article and Find Full Text PDFAnti-arthritic Effects of Undifferentiated and Chondrogenic Differentiated MSCs in MIA-induced Osteoarthritis in Wistar Rats: Involvement of Oxidative Stress and Immune Modulation.
Curr Stem Cell Res Ther
January 2025
Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
Introduction: Osteoarthritis (OA) is a degenerative joint disease that can affect the many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical use at this time probably due to a lack of complete comprehension of the pathogenesis of the disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated and differentiated cells have gained much attention as they can efficiently promote tissue repair and regeneration.
View Article and Find Full Text PDFMid-term outcomes of elbow hemiarthroplasty using the triceps-on approach for comminuted distal humerus fractures.
J Clin Orthop Trauma
February 2025
Trauma and Orthopaedics East and North Hertfordshire NHS Trust Lister Hospital, Stevenage, UK.
Background: There has been an increasing interest in elbow hemiarthroplasty to circumvent the problems with total elbow arthroplasty for comminuted distal humerus fractures in the elderly. The primary aim of the study is to assess the mid-term clinical and radiological outcomes of patients undergoing TEA and hemiarthroplasty for distal humerus fractures.
Methods: Retrospective analysis of data for patients undergoing hemiarthroplasty for distal humerus fractures (OTA- C3 Comminuted total articular fractures) was done.
Want 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!