ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
An activin A/BMP2 chimera, AB204, displays bone-healing properties superior to those of BMP2.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 43 citations in OpenAlex.
- Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.ACS biomaterials science & engineering · 2024Review
- Comparison of the biocompatibility and osteogenesis potential of whitlockite and an activin A/BMP2 chimera using a rat calvarial defect model: a pilot study.Journal of periodontal & implant science · 2024Article
- The activin/BMP-2 chimera AB204 promotes periodontal tissue regeneration in a buccal dehiscence model: a pilot study.Journal of periodontal & implant science · 2024Article
- Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects.Journal of periodontal & implant science · 2024Article
- Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment.Bioactive materials · 2023Article
- Small blood stem cells for enhancing early osseointegration formation on dental implants: a human phase I safety study.Stem cell research & therapy · 2021Article
- Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Investigational growth factors utilized in animal models of spinal fusion: Systematic review.World journal of orthopedics · 2019Article
- Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2.Journal of Korean Neurosurgical Society · 2018Article
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
- Structural Biology and Evolution of the TGF-β Family.Cold Spring Harbor perspectives in biology · 2016Review
- A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives.Stem cells international · 2016Review
- The effects of a single intravenous injection of novel activin A/BMP-2 (AB204) on toxicity and the respiratory and central nervous systems.Drug and chemical toxicology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures.
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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.