Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/Hedgehog signaling than that from normal bone
Affiliations 1 National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China. 2 Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 3 Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China. 4 Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. 5 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Traumatic heterotopic ossification refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues an...更多
Traumatic heterotopic ossification refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues and identified their stemness and multi-directional differentiation potential. Using alkaline phosphatase staining together with alizarin red staining, we confirmed that the HO-ops in the heterotopic ossified tissues gained greater osteogenic potential than the normal human bone marrow mesenchymal stem cells . RT-qPCR also indicated that HO-ops obtained more gene transcriptions of critical osteogenic determinators than HBMSCs. In addition, through Western blot, we proved that ERK signaling pathway and Hedgehog signaling pathway were significantly activated in the HO-ops. When U0126 and cyclopamine were used to inhibit ERK and hedgehog signaling respectively, the osteogenic potential of HO-ops decreased significantly. The hedgehog signaling and ERK signaling also showed cross-talk in HO-ops during osteogenic differentiation in HO-ops during osteogenic differentiation. The elevated ERK and hedgehog signaling was further confirmed in the human traumatic HO sample sections by immunohistochemical staining. In sum, our results showed that the activation of ERK and Hedgehog signaling pathway jointly enhanced the osteogenic potential of HO-ops to induce the formation of traumatic HO, which provides novel insights into the molecular basis of HO formation and offers promising targets for future therapeutic strategy. This article is protected by copyright. All rights reserved.收起
发文期刊《Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/Hedgehog signaling than that from normal bone》历年引证文献趋势图
