Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation.
"HMGB2 was detected at higher levels in human MSC as compared with human articular chondrocytes, and its expression declined during chondrogenic differentiation of MSC. Lentiviral HMGB2 transduction of MSC suppressed chondrogenesis as reflected by an inhibition of Col2a1 and Col10a1 expression. In bone marrow MSC from Hmgb2(-/-) mice, Col10a1 was more strongly expressed than in wild-type MSC. In vivo results from mouse growth plates [showed] that Hmgb2 is expressed in proliferating and prehypertrophic zones but not in hypertrophic cartilage where Col10a1 is strongly expressed. Osteogenesis was accelerated in Hmgb2(-/-) MSC. The expression of Runx2, which plays a major role in late stage chondrocyte differentiation, was enhanced in Hmgb2(-/-) MSC, and HMGB2 negatively regulated the stimulatory effect of Wnt/β-catenin signaling on the Runx2 proximal promoter."
Thus the downregulation of HMGB2 by LSJL is consistent with LSJL inducing chondrogenic differentiation.
"HMGB2's [inhibition of] chondrogenesis is related to binding with LEF1 and suppression of RUNX2."
"Ectopic expression of HMGB2 in human MSC suppressed Runx2 expression. HMGB2 repressed the augmentation of Runx2 promoter activity by co-transfection of β-catenin and LEF1."
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