Figure 2. Hypothetic pathogenesis of OPLL. Aberrant activation of BMP and TGF-β signaling plays a central role in development of OPLL.

Many pathological alterations, including mechanical stress, inflammatory response, transcriptional and pathway negative regulations, and genetic mutations, can cause activation of BMP and TGF-β signaling. As a result, Smads/Smad4 and MAPK are upregulated and transcriptions of Sox9, Runx2 and Osterix are increased, which modulates the differentiation and proliferation of MSCs, osteoblasts and chondrocytes and ultimately causes OPLL formation and advancement.