Gremlin-1 suppression increases BMP-2-induced osteogenesis of human mesenchymal stem cells
Kongzu Hu1, Heyan Sun1, Binjie Gui1
1Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
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.
Insights
Gremlin-1 suppresses osteogenesis in human mesenchymal stem cells (MSCs). Inhibiting gremlin-1 enhances MSC viability and bone formation, offering potential therapeutic targets for bone regeneration.
Area of Science:
- Stem cell biology
- Bone biology
- Molecular biology
Background:
- Gremlin-1 is known to inhibit osteogenesis in rodent models by antagonizing bone morphogenetic proteins (BMPs).
- The role of gremlin-1 in human bone marrow-derived mesenchymal stem cells (MSCs) osteogenesis is not well understood.
Purpose of the Study:
- To investigate the effect of gremlin-1 on the viability and osteogenic differentiation of human MSCs.
- To determine if gremlin-1 inhibition can enhance BMP-2-induced osteogenesis in human MSCs.
Main Methods:
- Used gremlin-1-specific small interfering RNA (siRNA) to inhibit gremlin-1 expression in human MSCs.
- Assessed cell viability, DNA content, osteoblastic gene expression via RT-qPCR, alkaline phosphatase (ALP) activity, and calcium deposition.
- Evaluated BMP-2-induced osteogenic differentiation.
Main Results:
- Gremlin-1 suppression significantly increased human MSC metabolism and DNA content.
- Inhibition of gremlin-1 led to significantly increased expression of osteoblastic genes.
- Gremlin-1 suppression significantly enhanced enzymatic ALP activity and calcium deposition in BMP-2-treated human MSCs.
Conclusions:
- Gremlin-1 inhibits cell viability and osteogenic differentiation in human MSCs.
- Suppression of gremlin-1 expression enhances BMP-2-induced osteogenic differentiation and viability of human MSCs.
- Targeting gremlin-1 may represent a therapeutic strategy for promoting bone formation.
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