title: Macrophages derived from THP-1 promote the osteogenic differentiation of mesenchymal stem cells through the IL-23/IL-23R/β-catenin pathway.
abstract: Abnormal bone formation is a clinically significant dilemma for many conditions in response to injury, inflammation or genetic disease. However, the effects of inflammation on the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. IL-23 secretion from macrophages might contribute to the development of bone formation. Here, we investigated the stimulatory effects of THP-1 macrophage conditioned medium (MΦ CM) on the osteogenic differentiation of human MSCs and the associated signaling pathways. The osteogenic differentiation of MSCs was induced after exposure to osteogenic differentiation medium (OM). MΦ CM significantly increased alkaline phosphate (ALP) activity and calcium mineralization in MSCs. Osteogenic marker genes, including RUNX2, ALP and osteocalcin (OCN), were also up-regulated in MSCs after exposure to MΦ CM. Moreover, western blotting revealed that MΦ CM treatment induced STAT3 and β-catenin activation in MSCs. Furthermore, blockade of IL-23 in MΦ CM not only impaired the osteogenic-promotion effects of macrophage but also decreased the expression of osteogenic maker genes. However, IL-23R silencing suppressed MΦ CM-induced calcium mineralization and osteogenic maker gene expression in MSCs. These data suggest that macrophages derived from THP-1 promote the osteoblastic differentiation of MSCs through the IL-23/IL-23R/β-catenin pathway and macrophages might contribute to the development of bone formation in inflammation.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, the Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Xuzhou Hospital (Affiliated with Medical College of Southeast University), Jiangsu 221009, China.
authors.forename: Guangwang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Bone and Joint Surgery, Wendeng Orthopaedic Hospital of Shandong Province, Shandong 264400, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China. Electronic address: fancunyi888@163.com.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; C515500:IL23R protein, human; D053759:Interleukin-23; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D051176:beta Catenin; D000469:Alkaline Phosphatase
keywords: IL-23; Inflammation; Macrophages; Mesenchymal stem cells; Osteogenic differentiation