ArticleBritish journal of pharmacology2011
Protein isoprenylation regulates osteogenic differentiation of mesenchymal stem cells: effect of alendronate, and farnesyl and geranylgeranyl transferase inhibitors.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 35 citations in OpenAlex.
- Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.The Journal of allergy and clinical immunology · 2019Trial
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Farnesyltransferase inhibitors decrease matrix-vesicle-mediated mineralization in SaOS-2 cells.Molecular biology reports · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- Lamin A and the LINC complex act as potential tumor suppressors in Ewing Sarcoma.Cell death & disease · 2022Article
- Multiple Porous Synthetic Bone Graft Comprising EngineeredMicro-Channel for Drug Carrier and Bone Regeneration.Materials (Basel, Switzerland) · 2021Article
- Role of Metabolism in Bone Development and Homeostasis.International journal of molecular sciences · 2020Review
- The role of lamin A/C in mesenchymal stem cell differentiation.Journal of physiology and biochemistry · 2019Review
- FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis.PloS one · 2018Article
- The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model.International journal of molecular sciences · 2015Article
- Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease.Pharmacology & therapeutics · 2014Review
- The susceptive alendronate-treatment timing and dosage for osteogenesis enhancement in human bone marrow-derived stem cells.PloS one · 2014Article
- Mechanisms of bone anabolism regulated by statins.Bioscience reports · 2012Review
- Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment.Histochemistry and cell biology · 2012Article
- Role of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis.BoneKEy reports · 2012Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeProtein isoprenylation is an important step in the intracellular signalling pathway conducting cell growth and differentiation. In bone, protein isoprenylation is required for osteoclast differentiation and activation. However, its role in osteoblast differentiation and function remains unknown. In this study, we assessed the role of protein isoprenylation in osteoblastogenesis in a model of mesenchymal stem cells (MSC) differentiation. EXPERIMENTAL APPROACH: We tested the effect of an inhibitor of farnesylation [farnesyl transferase inhibitor-277 (FTI-277)] and one of geranylgeranylation [geranylgeranyltransferase inhibitor-298 (GGTI-298)] on osteoblast differentiating MSC. In addition, we tested the effect of alendronate on protein isoprenylation in this model either alone or in combination with other inhibitors of isoprenylation. KEY
resultsInitially, we found that levels of unfarnesylated proteins (prelamin A and HDJ-2) increased after treatment with FTI-277 concomitantly affecting osteoblastogenesis and increasing nuclear morphological changes without affecting cell survival. Furthermore, inhibition of geranylgeranylation by GGTI-298 alone increased osteoblastogenesis. This effect was enhanced by the combination of GGTI-298 and alendronate in the osteogenic media. CONCLUSIONS AND IMPLICATIONS: Our data indicate that both farnesylation and geranylgeranylation play a role in osteoblastogenesis. In addition, a new mechanism of action for alendronate on protein isoprenylation in osteogenic differentiating MSC in vitro was found. In conclusion, protein isoprenylation is an important component of the osteoblast differentiation process that could constitute a new therapeutic target for osteoporosis in the future.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.