title: The Wnt5a/Ror2 pathway is associated with determination of the differentiation             fate of bone marrow mesenchymal stem cells in vascular calcification.
abstract: Accumulating evidence have demonstrated that mesenchymal stem cells (MSCs)             are involved in the initiation and progression of various vascular diseases. Canonical             Wnt signaling controls the fate of MSCs, and plays an important role in vascular             calcification. However, vascular calcification can be inhibited by the non-canonical             Wnt signaling pathway Wnt5a/Ror2. This study aimed to investigate whether the             Wnt5a/Ror2 pathway is associated with determination of the differentiation fate             of MSCs in vascular calcification. Direct co-cultures were established by seeding             smooth muscle cells (SMCs) or calcified SMCs and MSCs together at ratios of SMCs             or calcified SMCs 15x104; SMCs or calcified SMCs 5x104: MSCs 10x104, SMCs or calcified             SMCs 10x104: MSCs 5x104. Osteosynthesis-inducing medium (OS) was added to the             culture medium in the groups of MSCs with non-calcified SMCs. Cells were cultured             for nine days. Osteoblastic differentiation was evaluated by cell morphology and             the activity of alkaline phosphatase (ALP) in cell lysates and ALP staining. Furthermore,             we investigated the inhibition of Wnt signaling, and observed that the members             of the non-canonical signaling pathway Wnt5a/Ror2 were expressed in each group.             Additionally, MSCs cultured in culture media with OS did not differentiate into             an osteoblast phenotype when in direct contact with non-calcified SMCs, irrespective             of the number of MSCs. However, an osteoblast phenotype was observed when MSCs             were cultured in media without OS differentiation towards direct contact with             calcified SMCs, and the levels of osteoblastic markers had a direct correlation             with the number of MSCs. Of note, the Wnt5a protein was associated with the levels             of calcification, thus, although rarely detected in non-calcification, Ror2 mRNA             in the non-calcified groups was significantly higher compared to that in the calcified             groups. Therefore, the Wnt5a/Ror2 pathway is associated with determination of             the differentiation fate of bone marrow mesenchymal stem cells in vascular calcification.
authors: Department of Geriatrics, Union Hospital, Huazhong University of Science and Technology, Wuhan, PR China.
authors: Huaping
authors: H
authors: Xin
authors: Fang
authors: F
authors: Xin
authors: Shaoqiong
authors: S
authors: Zhou
authors: Siming
authors: S
authors: Guan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002113:Calcification, Physiologic; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D061205:Vascular Calcification / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: D012333:RNA, Messenger; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C500913:Ror2 protein, rat; D000469:Alkaline Phosphatase