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Fig. 6 | Journal of Experimental Orthopaedics

Fig. 6

From: Exposure of primary osteoblasts to combined magnetic and electric fields induced spatiotemporal endochondral ossification characteristic gene- and protein expression profiles

Fig. 6

Suggested signalling pathway for EFMF-induced endochondral ossification. Primary osteoblasts are characterized by high constitutive wnt- and TGFß1- (TGFB1) signaling. The latent TGFB1 converts to its active form under control of trombospondin 1 (THBS1). Active TGFB1 binds to its receptor TGFBR1 and regulates expression of ßIG-H3, which is a negative regulator of endochondral ossification. EFMF exposure increases calcium channel expression and results in Ca2+ influx. This increased Ca2+ levels activate protein kinase A (PKA). Activated PKA can phosphorylate catenin beta 1(CTNNB1), which prevents its degradation. The stabilized transcription factor CTNNB1 blocks THBS1-expression and subsequently TGFB1 activation. Reduced TGFB1 activation and EFMF induced reduced TGFB1 expression decreased TGFB1-signalling. This results in reduced expression of the inhibitor ßIG-H3 and stimulation of endochondral ossification. Endochondral ossification linked differentiation is characterized by increased expression of collagen type X (COL10A1), decorin (DCN), annexin A5 (ANXA5), osteopontin (SPP1), cathepsin K (CTSK), hypoxia inducible factor 1 subunit α (HIF1A), vascular entothelial growth factor B (VEGFB), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 5A (COX5A), ATP synthase F1 subunit alpha (ATP5A1). and increased Ca-deposition (Fig. 5)

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