ArticleThe Journal of cell biology2019
Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth.
Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Primary cilia in growth plates orchestrate long bone development.Fundamental research · 2025Article
- Mechanical forces remodel the cardiac extracellular matrix during zebrafish development.Development (Cambridge, England) · 2024Article
- Enhanced bone regeneration via endochondral ossification using Exendin-4-modified mesenchymal stem cells.Bioactive materials · 2024Article
- Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.Frontiers in pharmacology · 2023Review
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Genome-Wide Estimates of Runs of Homozygosity, Heterozygosity, and Genetic Load in Two Chinese Indigenous Goat Breeds.Frontiers in genetics · 2022Article
- Roles of the fibroblast growth factor signal transduction system in tissue injury repair.Burns & trauma · 2022Review
- Runx2 is required for hypertrophic chondrocyte mediated degradation of cartilage matrix during endochondral ossification.Matrix biology plus · 2021Article
- Abnormal B-cell development in TIMP-deficient bone marrow.Blood advances · 2021Article
- Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis.Calcified tissue international · 2021Review
- Dysregulated ECM remodeling proteins lead to aberrant osteogenesis of Costello syndrome iPSCs.Stem cell reports · 2021Article
- Concepts of extracellular matrix remodelling in tumour progression and metastasis.Nature communications · 2020Review
- Aggrecanase-selective tissue inhibitor of metalloproteinase-3 (TIMP3) protects articular cartilage in a surgical mouse model of osteoarthritis.Scientific reports · 2020Article
- Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Regulated growth plate activity is essential for postnatal bone development and body stature, yet the systems regulating epiphyseal fusion are poorly understood. Here, we show that the tissue inhibitors of metalloprotease (TIMP) gene family is essential for normal bone growth after birth. Whole-body quadruple-knockout mice lacking all four TIMPs have growth plate closure in long bones, precipitating limb shortening, epiphyseal distortion, and widespread chondrodysplasia. We identify TIMP/FGF-2/IHH as a novel nexus underlying bone lengthening where TIMPs negatively regulate the release of FGF-2 from chondrocytes to allow IHH expression. Using a knock-in approach that combines MMP-resistant or ADAMTS-resistant aggrecans with TIMP deficiency, we uncouple growth plate activity in axial and appendicular bones. Thus, natural metalloprotease inhibitors are crucial regulators of chondrocyte maturation program, growth plate integrity, and skeletal proportionality. Furthermore, individual and combinatorial TIMP-deficient mice demonstrate the redundancy of metalloprotease inhibitor function in embryonic and postnatal development.
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Registered trials
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