ArticlePloS one2014
Partial agonist, telmisartan, maintains PPARγ serine 112 phosphorylation, and does not affect osteoblast differentiation and bone mass.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Effects of telmisartan and losartan treatments on bone turnover markers in patients with newly diagnosed stage I hypertension.Journal of the renin-angiotensin-aldosterone system : JRAASTrial
- The Placenta Regulates Intrauterine Fetal Growth via Exosomal PPARγ.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Anti-Obesity Drug Delivery Systems: Recent Progress and Challenges.Pharmaceutics · 2023Review
- Dendrobium mixture ameliorates type 2 diabetes mellitus with non-alcoholic fatty liver disease through PPAR gamma: An integrated study of bioinformatics analysis and experimental verification.Frontiers in pharmacology · 2023Article
- Emodin attenuates severe acute pancreatitis-associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation.Acta pharmaceutica Sinica. B · 2022Article
- The Role of Peroxisome Proliferator-Activated Receptor Gamma and Atherosclerosis: Post-translational Modification and Selective Modulators.Frontiers in physiology · 2022Review
- Transdermal Drug Delivery Systems and Their Use in Obesity Treatment.International journal of molecular sciences · 2021Review
- The Antihypertensive Drug Telmisartan Protects Oligodendrocytes from Cholesterol Accumulation and Promotes Differentiation by a PPAR-γ-Mediated Mechanism.International journal of molecular sciences · 2021Article
- The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue.Pharmaceuticals (Basel, Switzerland) · 2021Article
- PPARγ and Diabetes: Beyond the Genome and Towards Personalized Medicine.Current diabetes reports · 2021Review
- Ectopic Overexpression of PPARγ2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes.Frontiers in pharmacology · 2021Article
- The PPARPPAR research · 2020Review
- miRNA‑15a‑5p facilitates the bone marrow stem cell apoptosis of femoral head necrosis through the Wnt/β‑catenin/PPARγ signaling pathway.Molecular medicine reports · 2019Article
- Telmisartan induces browning of fully differentiated white adipocytes via M2 macrophage polarization.Scientific reports · 2019Article
- CMHX008, a PPARγ partial agonist, enhances insulin sensitivity with minor influences on bone loss.Genes & diseases · 2018Article
- Marrow Fat-a New Target to Treat Bone Diseases?Current osteoporosis reports · 2018Review
- N-Acetylcysteine (NAC) Ameliorates Lipid-Related Metabolic Dysfunction in Bone Marrow Stromal Cells-Derived Adipocytes.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Deciphering the Roles of PPARγ in Adipocytes via Dynamic Change of Transcription Complex.Frontiers in endocrinology · 2018Review
- Marrow Adipose Tissue: Skeletal Location, Sexual Dimorphism, and Response to Sex Steroid Deficiency.Frontiers in endocrinology · 2017Article
- PPARG Post-translational Modifications Regulate Bone Formation and Bone Resorption.EBioMedicine · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Peroxisome proliferator activated receptor gamma (PPARγ) controls both glucose metabolism and an allocation of marrow mesenchymal stem cells (MSCs) toward osteoblast and adipocyte lineages. Its activity is determined by interaction with a ligand which directs posttranscriptional modifications of PPARγ protein including dephosphorylation of Ser112 and Ser273, which results in acquiring of pro-adipocytic and insulin-sensitizing activities, respectively. PPARγ full agonist TZD rosiglitazone (ROSI) decreases phosphorylation of both Ser112 and Ser273 and its prolonged use causes bone loss in part due to diversion of MSCs differentiation from osteoblastic toward adipocytic lineage. Telmisartan (TEL), an anti-hypertensive drug from the class of angiotensin receptor blockers, also acts as a partial PPARγ agonist with insulin-sensitizing and a weak pro-adipocytic activity. TEL decreased S273pPPARγ and did not affect S112pPPARγ levels in a model of marrow MSC differentiation, U-33/γ2 cells. In contrast to ROSI, TEL did not affect osteoblast phenotype and actively blocked ROSI-induced anti-osteoblastic activity and dephosphorylation of S112pPPARγ. The effect of TEL on bone was tested side-by-side with ROSI. In contrast to ROSI, TEL administration did not affect bone mass and bone biomechanical properties measured by micro-indentation method and did not induce fat accumulation in bone, and it partially protected from ROSI-induced bone loss. In addition, TEL induced "browning" of epididymal white adipose tissue marked by increased expression of UCP1, FoxC2, Wnt10b and IGFBP2 and increased overall energy expenditure. These studies point to the complexity of mechanisms by which PPARγ acquires anti-osteoblastic and pro-adipocytic activities and suggest an importance of Ser112 phosphorylation status as being a part of the mechanism regulating this process. These studies showed that TEL acts as a full PPARγ agonist for insulin-sensitizing activity and as a partial agonist/partial antagonist for pro-adipocytic and anti-osteoblastic activities. They also suggest a relationship between PPARγ fat "browning" activity and a lack of anti-osteoblastic activity.
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