ArticleThe Journal of biological chemistry2023
Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.
Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming.Nature communications · 2025Article
- GLP-1RA in JBMMSCs promoted osteogenic differentiation via modulating CREB and BRD4 signaling mediated proliferation and stemness.Scientific reports · 2025Article
- MGP regulates the adipogenic differentiation of mesenchymal stem cells in osteoporosis via the Ca2+/CaMKII/RIP140/FABP3 axis.Cell death discovery · 2025Article
- Exploring the association between circadian rhythms and osteoporosis: new diagnostic and therapeutic targets identified via machine learning.Frontiers in molecular biosciences · 2025Article
- LEP O-GlcNAcylation inactivates NF-κB pathway by suppressing LEP protein level and thus mediates cellular senescence and osteogenic differentiation in mouse mesenchymal stem cells.BMC molecular and cell biology · 2024Article
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12 authors at 2 institutions in 1 country.
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Abstract
An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis.
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