Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis

• Published in: International journal of molecular sciences Vol. 20; no. 10; p. 2500
• Main Authors: Vrathasha, Vrathasha, Weidner, Hilary, Nohe, Anja
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.05.2019; MDPI
• Subjects: Animals; Apposition; Binding sites; Biomedical materials; BMP2; bone; Bone density; Bone Marrow Cells - metabolism; Bone mineral density; Bone morphogenetic protein 2; Bone Morphogenetic Protein Receptors, Type I - metabolism; Bone resorption; Calvaria; Cell Line; CK2; CK2.3; Female; Fractures; Genes; Human parathyroid hormone; Hyperparathyroidism; Injection; Kinases; MAP Kinase Signaling System; Mice; Mimicry; Mineralization; Mutants; Osteoclasts; Osteogenesis; Osteogenesis - drug effects; osteogenic signal transduction; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - metabolism; Osteoporosis - physiopathology; Parathyroid; Parathyroid hormone; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptides; Phosphatase; Phosphorylation; Proteins; RT-qPCR; Serine; Signal Transduction; Smad Proteins, Receptor-Regulated - metabolism; western blots; western blots; BMP2; bone; CK2; osteogenesis; CK2.3; osteogenic signal transduction; osteoporosis; RT-qPCR
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20102500

Osteoporosis is a degenerative skeletal disease with a limited number of treatment options. CK2.3, a novel peptide, may be a potential therapeutic. It induces osteogenesis and bone formation in vitro and in vivo by acting downstream of BMPRIA through releasing CK2 from the receptor. However, the detailed signaling pathways, the time frame of signaling, and genes activated remain largely unknown. Using a newly developed fluorescent CK2.3 analog, specific inhibitors for the BMP signaling pathways, Western blot, and RT-qPCR, we determined the mechanism of CK2.3 in C2C12 cells. We then confirmed the results in primary BMSCs. Using these methods, we showed that CK2.3 stimulation activated , , and . CK2.3 stimulation induced time dependent release of CK2β from BMPRIA and concurrently CK2.3 colocalized with CK2α. Furthermore, CK2.3 induced BMP signaling depends on ERK1/2 and Smad1/5/8 signaling pathways. CK2.3 is a novel peptide that drives osteogenesis, and we detailed the molecular sequence of events that are triggered from the stimulation of CK2.3 until the induction of mineralization. This knowledge can be applied in the development of future therapeutics for osteoporosis.