ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
A new MMP-mediated prodomain cleavage mechanism to activate bone morphogenetic proteins from the extracellular matrix.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Systems Biology and Experimental Validation Enable Discovery of MMP9-Centered Networks, Anticancer Activity, and Pharmacodynamic Signature in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Analysis of the Matrix Metalloproteinases Family Profile in Gastric Cancer Suggests Key Matrix Metalloproteinases for Tumor Development and Their Clinical Impact.Molecular carcinogenesis · 2026Article
- Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the development of Charcot arthropathy.Acta diabetologica · 2026Article
- Caspase-1 Mediated Cleavage of BMP Type I Receptor Drives BMP2-Induced Differentiation of Bone Marrow Mesenchymal Stem Cells into Adipocytes.Applied sciences (Basel, Switzerland) · 2025Article
- POGLUT2/3 mediated EGF O-glucosylation promotes separation of digits 2 and 3 by influencing fibrillin network reorganization, signaling, and cell dynamics.Developmental biology · 2025Article
- Prodomain processing controls BMP-10 bioactivity and targeting to fibrillin-1 in latent conformation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- New insights into the structural role of EMILINs within the human skin microenvironment.Scientific reports · 2024Article
- The importance of BMPs and TGF-βs for endochondral bone repair - A longitudinal study in hip arthroplasty patients.Bone reports · 2023Article
- The extracellular matrix glycoprotein fibrillin-1 in health and disease.Frontiers in cell and developmental biology · 2023Review
- Article
- The role of pro-domains in human growth factors and cytokines.Biochemical Society transactions · 2021Review
- A new MMP-mediated prodomain cleavage mechanism to activate bone morphogenetic proteins from the extracellular matrix.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
Corrections and comments
- Erratum issuedErratum.2022
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Since their discovery as pluripotent cytokines extractable from bone matrix, it has been speculated how bone morphogenetic proteins (BMPs) become released and activated from the extracellular matrix (ECM). In contrast to TGF-βs, most investigated BMPs are secreted as bioactive prodomain (PD)-growth factor (GF) complexes (CPLXs). Recently, we demonstrated that PD-dependent targeting of BMP-7 CPLXs to the extracellular fibrillin microfibril (FMF) components fibrillin-1 and -2 represents a BMP sequestration mechanism by rendering the GF latent. Understanding how BMPs become activated from ECM scaffolds such as FMF is crucial to elucidate pathomechanisms characterized by aberrant BMP activation and ECM destruction. Here, we describe a new MMP-dependent BMP-7 activation mechanism from ECM-targeted pools via specific PD degradation. Using Edman sequencing and mutagenesis, we identified a new and conserved MMP-13 cleavage site within the BMP-7 PD. A degradation screen with different BMP family PDs and representative MMP family members suggested utilization of the identified site in a general MMP-driven BMP activation mechanism. Furthermore, sandwich ELISA and solid phase cleavage studies in combination with bioactivity assays, single particle TEM, and in silico molecular docking experiments provided evidence that PD cleavage by MMP-13 leads to BMP-7 CPLX disintegration and bioactive GF release.
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