ArticlePloS one2014
Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting MDK alleviates bone loss via dual regulation of osteogenic differentiation and inflammatory cytokine expression.Genes & diseases · 2026Article
- Piezo1 in hypertrophic chondrocytes regulates osteoclastogenesis in endochondral ossification.International journal of biological sciences · 2026Article
- Exploring drug resistance via intercellular crosstalk using spatial transcriptomics in high-grade serous ovarian carcinoma.NPJ precision oncology · 2025Article
- Metabolic reprogramming of arachidonic acid in clear cell renal carcinoma promotes an immunosuppressive microenvironment by activating MDK signaling pathway.Clinical and experimental medicine · 2025Article
- EGFRvIII-positive glioblastoma contributes to immune escape and malignant progression via the c-Fos-MDK-LRP1 axis.Cell death & disease · 2025Article
- TSG-6 promotes healing of critical-sized bone defects in mice.Frontiers in immunology · 2025Article
- Immunomodulation Pathogenesis and Treatment of Bone Nonunion.Orthopaedic surgery · 2024Review
- Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.European journal of breast health · 2024Article
- Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells.iScience · 2024Article
- Complement receptor C5aR1 on osteoblasts regulates osteoclastogenesis in experimental postmenopausal osteoporosis.Frontiers in endocrinology · 2022Article
- Mast Cells Drive Systemic Inflammation and Compromised Bone Repair After Trauma.Frontiers in immunology · 2022Article
- Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing.Frontiers in bioengineering and biotechnology · 2021Article
- Acute kidney injury risk in orthopaedic trauma patients pre and post surgery using a biomarker algorithm and clinical risk score.Scientific reports · 2020Article
- A single cell transcriptional atlas of early synovial joint development.Development (Cambridge, England) · 2020Article
- Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.Oncogene · 2020Review
- Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model.Scientific reports · 2019Article
- Chronic psychosocial stress compromises the immune response and endochondral ossification during bone fracture healing via β-AR signaling.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Pharmacological inhibition of IL-6 trans-signaling improves compromised fracture healing after severe trauma.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- The Role of the Intestinal Microbiome in Chronic Psychosocial Stress-Induced Pathologies in Male Mice.Frontiers in behavioral neuroscience · 2018Article
- Chronic psychosocial stress disturbs long-bone growth in adolescent mice.Disease models & mechanisms · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The growth and differentiation factor midkine (Mdk) plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.