Ossification of the Pposterior Longitudinal Ligament

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To understand the molecular pathogenesis of ossification of the posterior longitudinal ligament of the spine (OPLL), an ectopic bone formation disease, we performed c_DNA microarray analysis on cultured ligament cells from the OPLL patients to understand the molecular pathogenesis of OPLL.We identified Zinc finger protein145 (PLZF) as one of up-regulated genes and tumor necrosis factor-a stimulated gene6 (TSG-6) and one of down-regulated gene during osteoblastic differentiation. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of h_MSC_s and C2C12 cells.siRNA-mediated gene-silencing of PLZF resulted in a reduction of the expression of osteoblast-specific genes such as the alkaline phosphatase (ALP), collagen 1A1 (COL1A1), Runx2/cbfal (CBFA1), and osteocalcin (OCN) genes in the presence of OS in hMSCs.The overexpression of PLZF can induce CBFA1 induction suggestiong PLZF is an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients. Adenoirus-mediated TSG-6 overexpression in hMSCs resulted in suppression of oseoblastic differentiation induced by either BMP-2 or OS.TSG-6 can bind to BMP-2 directly, thereby could inhibit BMP-2 signaling.Taken together, these findings indicate that PLZF and TSG-6 play important roles in early osteoblastic differentiation.