ArticleInternational journal of molecular sciences2016
CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Single-Cell Transcriptomics Reveals Riluzole as an Osteoarthritis Candidate Drug via OB-NE Signaling Modulation and CTSS/NOS1 Inhibition.Drug design, development and therapy · 2026Article
- Targeting the CXCL12/CXCR4 pathway by an optimized derivative or EPI-X4 preserves chondrocyte function and offers a novel therapeutic approach in rheumatic diseases.Arthritis research & therapy · 2025Article
- Therapeutic potential of SOX family transcription factors in osteoarthritis.Annals of medicine · 2025Review
- Identification and experimental verification of biomarkers related to butyrate metabolism in osteoarthritis.Scientific reports · 2025Article
- Serum CXCL12 and S100A12 levels in peripheral blood fluid and their correlation with severity in patients with knee osteoarthritis.Journal of medical biochemistry · 2025Article
- Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis.Heliyon · 2024Article
- Chemokines in Cartilage Regeneration and Degradation: New Insights.International journal of molecular sciences · 2023Review
- Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis.Journal of orthopaedic surgery and research · 2023Review
- CXCL12 and CXCR4 as Novel Biomarkers in Uric Acid-Induced Inflammation and Patients with Gouty Arthritis.Biomedicines · 2023Article
- Rongjin Niantong Fang ameliorates cartilage degeneration by regulating the SDF-1/CXCR4-p38MAPK signalling pathway.Pharmaceutical biology · 2022Article
- Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig.Journal of orthopaedic surgery and research · 2021Article
- Knockdown of long noncoding RNA HOTAIR inhibits osteoarthritis chondrocyte injury by miR-107/CXCL12 axis.Journal of orthopaedic surgery and research · 2021Article
- Quercitrin alleviates cartilage extracellular matrix degradation and delays ACLT rat osteoarthritis development: An in vivo and in vitro study.Journal of advanced research · 2021Article
- G Protein-Coupled Receptors in Osteoarthritis.Frontiers in endocrinology · 2021Review
- Neferine Inhibits Expression of Inflammatory Mediators and Matrix Degrading Enzymes in IL-1β-Treated Rat Chondrocytes via Suppressing MAPK and NF-κB Signaling Pathways.Inflammation · 2020Article
- miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway.Biochemistry research international · 2020Article
- NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway.Journal of cellular and molecular medicine · 2019Article
- CXCL12/CXCR4 signaling contributes to neuropathic pain via central sensitization mechanisms in a rat spinal nerve ligation model.CNS neuroscience & therapeutics · 2019Article
- SDF1/CXCR4 axis plays a role in angiogenesis during the degeneration of intervertebral discs.Molecular medicine reports · 2019Article
- Costunolide inhibits matrix metalloproteinases expression and osteoarthritis via the NF‑κB and Wnt/β‑catenin signaling pathways.Molecular medicine reports · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/β-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.
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