title: Gremlin-1 suppression increases BMP-2-induced osteogenesis of human mesenchymal stem cells.
abstract: Previous research focusing on rodent cells and animal models has demonstrated that gremlin-1 antagonizes bone morphogenetic proteins (BMPs) in order to suppress osteogenesis. However, the impact of gremlin‑1 on osteogenesis in human bone marrow-derived mesenchymal stem cells (MSCs) remains unknown. The aim of the present study was to test the effects of gremlin-1 on viability and in vitro BMP-2-induced osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells (MSCs). Gremlin‑1‑specific small interfering RNA (siRNA) inhibited gremlin‑1 mRNA and protein expression in human MSCs. The mRNA expression levels of osteoblastic genes were analyzed using reverse transcription-quantitative polymerase chain reaction, and calcification and enzymatic alkaline phosphatase (ALP) activity assessed the BMP‑2‑induced osteogenic differentiation of human MSCs. The results indicated that gremlin‑1 suppression significantly increased human MSC metabolism and DNA content. The expression levels of osteoblastic genes were also significantly increased by gremlin‑1 inhibition. In the gremlin‑1‑inhibited group, enzymatic ALP activity was significantly increased. In addition, due to BMP‑2‑inducing osteoblasts, gremlin‑1 inhibition increased calcium deposits. The present study indicated that gremlin‑1 inhibited the cell viability and osteogenic differentiation of human MSCs and that the suppression of gremlin‑1 expression suppressed can increase the cell viability and osteogenic differentiation of human MSCs induced by BMP-2.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Kongzu
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Heyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Binjie
authors.initials: B
authors.lastname: Gui
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Sui
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering