ArticleThe Journal of biological chemistry2009
miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 242 citations in OpenAlex.
- Overcoming challenges in cartilage regeneration: The role of chondrogenic inducers.Bioengineering & translational medicine · 2026Review
- MicroRNA-mediated mechanotransduction and chondrocyte differentiation in mesenchymal stem cells.Animal cells and systems · 2026Review
- Role of Cytokines in Bone Diseases and Their Therapeutic Application.ImmunoTargets and therapy · 2026Review
- miR-199a functions downstream of MeCP2 in neurons ofiScience · 2025Article
- Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4/NF-κB signaling pathway to relieve osteoarthritis.World journal of stem cells · 2025Article
- miRNA-based regulation in growth plate cartilage: mechanisms, targets, and therapeutic potential.Frontiers in endocrinology · 2025Review
- Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis.eLife · 2024Article
- Molecular Signaling Pathways and MicroRNAs in Bone Remodeling: A Narrative Review.Diseases (Basel, Switzerland) · 2024Review
- Osteoporosis GWAS-implicatedJBMR plus · 2024Article
- Regulation of ferroptosis in osteoarthritis and osteoarthritic chondrocytes by typical MicroRNAs in chondrocytes.Frontiers in medicine · 2024Review
- Long Non-coding RNA DNM3OS: Pathogenic Roles and Molecular Mechanisms in Pathophysiological Processes.Current medicinal chemistry · 2024Review
- Review
- The Effect of miR-140-5p with HDAC4 towards Growth and Differentiation Signaling of Chondrocytes in Thiram-Induced Tibial Dyschondroplasia.International journal of molecular sciences · 2023Article
- MicroRNAs-mediated regulation pathways in rheumatic diseases.Inflammopharmacology · 2023Review
- Regulatory of miRNAs in tri-lineage differentiation of C3H10T1/2.Stem cell research & therapy · 2022Review
- The therapeutic effect and mechanism of melatonin on osteoarthritis: From the perspective of non-coding RNAs.Frontiers in genetics · 2022Review
- Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis.Molecular therapy. Nucleic acids · 2021Article
- Osteogenic and Chondrogenic Potential of Periosteum-Derived Mesenchymal Stromal Cells: Do They Hold the Key to the Future?Pharmaceuticals (Basel, Switzerland) · 2021Review
- Characterization and miRNA Profiling of Extracellular Vesicles from Human Osteoarthritic Subchondral Bone Multipotential Stromal Cells (MSCs).Stem cells international · 2021Article
- Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
MicroRNAs (miRNA) are short non-coding RNA molecules that regulate a variety of biological processes. The role of miRNAs in BMP2-mediated biological processes is of considerable interest. A comparative miRNA array led to the isolation of several BMP2-responsive miRNAs. Among them, miR-199a(*) is of particular interest, because it was reported to be specifically expressed in the skeletal system. Here we demonstrate that miR-199a(*) is an early responsive target of BMP2: its level was dramatically reduced at 5 h, quickly increased at 24 h and remained higher thereafter in the course of BMP2-triggered chondrogenesis of a micromass culture of pluripotent C3H10T1/2 stem cells. miR-199a(*) significantly inhibited early chondrogenesis, as revealed by the reduced expression of early marker genes for chondrogenesis such as cartilage oligomeric matrix protein (COMP), type II collagen, and Sox9, whereas anti-miR-199a(*) increased the expression of these chondrogenic marker genes. A computer-based prediction algorithm led to the identification of Smad1, a well established downstream molecule of BMP-2 signaling, as a putative target of miR-199a(*). The pattern of Smad1 mRNA expression exhibited the mirror opposite of miR-199a(*) expression following BMP-2 induction. Furthermore, miR-199a(*) demonstrated remarkable inhibition of both endogenous Smad1 as well as a reporter construct bearing the 3-untranslated region of Smad1 mRNA. In addition, mutation of miR-199a(*) binding sites in the 3'-untranslated region of Smad1 mRNA abolished miR-199a(*)-mediated repression of reporter gene activity. Mechanism studies revealed that miR-199a(*) inhibits Smad1/Smad4-mediated transactivation of target genes, and that overexpression of Smad1 completely corrects miR-199a(*)-mediated repression of early chondrogenesis. Taken together, miR-199a(*) is the first BMP2 responsive microRNA found to adversely regulate early chondrocyte differentiation via direct targeting of the Smad1 transcription factor.
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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.