AI Article Synopsis
- Noggin and sclerostin are proteins that inhibit bone morphogenetic proteins (BMPs), affecting their activity.
- They interact strongly with each other, as shown by experiments with both recombinant and naturally occurring forms of these proteins.
- Their complex can interfere with BMP binding and diminish the effects of each antagonist, suggesting a new way BMP activity is fine-tuned for maintaining bone health.
Article Abstract
Noggin and sclerostin are bone morphogenetic protein (BMP) antagonists that modulate mitogenic activity through sequestering BMPs. Little is known of the interactions among this class of proteins. We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm). This observation has been extended to naturally expressed noggin and sclerostin from the rat osteosarcoma cell line, ROS 17/2.8, supporting a role for the complex in natural systems. The noggin-sclerostin complex was competitive with BMP binding and mutually attenuated the activity of each BMP antagonist. Collectively, the data demonstrate a novel and exquisite paradigm for the regulation of BMP activity through direct neutralization of the BMP and activation by co-localized BMP antagonist expression. The pleiotrophic nature of noggin and sclerostin represents a novel mechanism for the fine-tuning of BMP activity in bone homeostasis.
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| http://dx.doi.org/10.1074/jbc.M400521200 | DOI Listing |
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