ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Direct In-Bone Protein Digestion With Subsequent LC Separation and Trap Ion Mobility MS Detection of Released Peptides as an Effective Tool for the Proteomic Characterization of Bone Tissues.Journal of separation science · 2025Article
- The Role of PEDF in the Eye, Bone, and Nervous and Immune Systems.Pharmaceutics · 2025Review
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.Journal of human genetics · 2023Article
- Bone Mass Accrual in First Six Months of Life: Impact of Maternal Diabetes, Infant Adiposity, and Cord Blood Adipokines.Calcified tissue international · 2022Article
- Antagonism Between PEDF and TGF-β Contributes to Type VI Osteogenesis Imperfecta Bone and Vascular Pathogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types.Endocrine reviews · 2022Review
- Pigment epithelium-derived factor (PEDF) reduced expression and synthesis of SOST/sclerostin in bone explant cultures: implication of PEDF-osteocyte gene regulation in vivo.Journal of bone and mineral metabolism · 2019Article
- Bone biology: insights from osteogenesis imperfecta and related rare fragility syndromes.The FEBS journal · 2019Review
- Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation.International journal of molecular sciences · 2019Article
- Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations.International journal of molecular sciences · 2019Review
- Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- WNT16 induces proliferation and osteogenic differentiation of human perivascular stem cells.Journal of orthopaedics · 2018Article
- miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes.Journal of lipid research · 2018Article
- Effects of WNT3A and WNT16 on the Osteogenic and Adipogenic Differentiation of Perivascular Stem/Stromal Cells.Tissue engineering. Part A · 2018Article
- The genetic implication of scoliosis in osteogenesis imperfecta: a review.Journal of spine surgery (Hong Kong) · 2017Review
- Review
- Challenges of bone tissue engineering in orthopaedic patients.World journal of orthopedics · 2017Article
- Pigment epithelium-derived factor (PEDF) normalizes matrix defects in iPSCs derived from Osteogenesis imperfecta Type VI.Rare diseases (Austin, Tex.) · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Null mutations in for pigment epithelium-derived factor (PEDF), the protein product of the SERPINF1 gene, are the cause of osteogenesis imperfecta (OI) type VI. The PEDF-knockout (KO) mouse captures crucial elements of the human disease, including diminished bone mineralization and propensity to fracture. Our group and others have demonstrated that PEDF directs human mesenchymal stem cell (hMSC) commitment to the osteoblast lineage and modulates Wnt/β-catenin signaling, a major regulator of bone development; however, the ability of PEDF to restore bone mass in a mouse model of OI type VI has not been determined. In this study, PEDF delivery increased trabecular bone volume/total volume by 52% in 6-mo-old PEDF-KO mice but not in wild-type mice. In young (19-d-old) PEDF-KO mice, PEDF restoration increased bone volume fraction by 35% and enhanced biomechanical parameters of bone plasticity. A Wnt-green fluorescent protein reporter demonstrated dynamic changes in Wnt/β-catenin signaling characterized by early activation and marked suppression during terminal differentiation of hMSCs. Continuous Wnt3a exposure impeded mineralization of hMSCs, whereas the combination of Wnt3a and PEDF potentiated mineralization. Interrogation of the PEDF sequence identified a conserved motif found in other Wnt modulators, such as the dickkopf proteins. Mutation of a single amino acid on a 34-mer PEDF peptide increased mineralization of hMSC cultures compared with the native peptide sequence. These results indicate that PEDF counters Wnt signaling to allow for osteoblast differentiation and provides a mechanistic insight into how the PEDF null state results in OI type VI.-Belinsky, G. S., Sreekumar, B., Andrejecsk, J. W., Saltzman, W. M., Gong, J., Herzog, R. I., Lin, S., Horsley, V., Carpenter, T. O., Chung, C. Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade.
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Registered trials
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