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2 "Lobeglitazone"
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Endocrine Research
Effects of Lobeglitazone, a New Thiazolidinedione, on Osteoblastogenesis and Bone Mineral Density in Mice
Kyoung Min Kim, Hyun-Jin Jin, Seo Yeon Lee, Hyo Jin Maeng, Gha Young Lee, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Soo Lim
Endocrinol Metab. 2017;32(3):389-395.   Published online September 18, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.3.389
  • 5,091 View
  • 52 Download
  • 11 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   
Background

Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone.

Methods

MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 µM), rosiglitazone (0.4 µM), or pioglitazone (1 µM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment.

Results

As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice.

Conclusion

These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
    Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697.     CrossRef
  • Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
    Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703.     CrossRef
  • A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
    Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
    Diabetes & Metabolism Journal.2022; 46(6): 855.     CrossRef
  • Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
    Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
    Diabetes Therapy.2021; 12(1): 171.     CrossRef
  • Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
    Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
    Diabetes & Metabolism Journal.2021; 45(3): 326.     CrossRef
  • Effect of lobeglitazone on motor function in rat model of Parkinson’s disease with diabetes co-morbidity
    Kambiz Hassanzadeh, Arman Rahimmi, Mohammad Raman Moloudi, Rita Maccarone, Massimo Corbo, Esmael Izadpanah, Marco Feligioni
    Brain Research Bulletin.2021; 173: 184.     CrossRef
  • Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus
    Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek
    Endocrinology and Metabolism.2021; 36(4): 895.     CrossRef
  • Xenogeneic native decellularized matrix carrying PPARγ activator RSG regulating macrophage polarization to promote ligament-to-bone regeneration
    Xue Han, Lijun Liao, Tian Zhu, Yuchan Xu, Fei Bi, Li Xie, Hui Li, Fangjun Huo, Weidong Tian, Weihua Guo
    Materials Science and Engineering: C.2020; 116: 111224.     CrossRef
  • Diabetes pharmacotherapy and effects on the musculoskeletal system
    Evangelia Kalaitzoglou, John L. Fowlkes, Iuliana Popescu, Kathryn M. Thrailkill
    Diabetes/Metabolism Research and Reviews.2019;[Epub]     CrossRef
  • The effects of diabetes therapy on bone: A clinical perspective
    Karim G. Kheniser, Carmen M. Polanco Santos, Sangeeta R. Kashyap
    Journal of Diabetes and its Complications.2018; 32(7): 713.     CrossRef
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Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
Kwi-Hyun Bae, Jung Beom Seo, Yun-A Jung, Hye-Young Seo, Sun Hee Kang, Hui-Jeon Jeon, Jae Man Lee, Sungwoo Lee, Jung-Guk Kim, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
Endocrinol Metab. 2017;32(1):115-123.   Published online February 28, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.115
  • 5,091 View
  • 80 Download
  • 13 Web of Science
  • 14 Crossref
AbstractAbstract PDFPubReader   
Background

Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice.

Methods

We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study.

Results

Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway.

Conclusion

The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.

Citations

Citations to this article as recorded by  
  • The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis
    Shiyan Jian, Kang Yang, Lingna Zhang, Limeng Zhang, Zhongquan Xin, Chaoyu Wen, Shansong He, Jinping Deng, Baichuan Deng
    Food Frontiers.2023; 4(1): 262.     CrossRef
  • Druggability of lipid metabolism modulation against renal fibrosis
    Yuan-yuan Chen, Xiao-guang Chen, Sen Zhang
    Acta Pharmacologica Sinica.2022; 43(3): 505.     CrossRef
  • Lobeglitazone attenuates fibrosis in corneal fibroblasts by interrupting TGF-beta-mediated Smad signaling
    Selikem Nuwormegbe, Na-Young Park, Sun Woong Kim
    Graefe's Archive for Clinical and Experimental Ophthalmology.2022; 260(1): 149.     CrossRef
  • Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
    Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
    Diabetes Therapy.2021; 12(1): 171.     CrossRef
  • Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
    Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
    Diabetes & Metabolism Journal.2021; 45(3): 326.     CrossRef
  • Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway
    Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim
    Endocrinology and Metabolism.2021; 36(5): 1095.     CrossRef
  • Protocol for a preclinical systematic review and meta-analysis of pharmacological targeting of peroxisome proliferator-activated receptors in experimental renal injury
    William P Martin, Yeong H D Chuah, Emer Conroy, Alison L Reynolds, Conor Judge, Francisco J López-Hernández, Carel W le Roux, Neil G Docherty
    BMJ Open Science.2021;[Epub]     CrossRef
  • Stevioside inhibits unilateral ureteral obstruction‐induced kidney fibrosis and upregulates renal PPARγ expression in mice
    Wei Shen, Ke Fan, Ying Zhao, Junyan Zhang, Meilin Xie
    Journal of Food Biochemistry.2020;[Epub]     CrossRef
  • FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose
    Chenlin Gao, Fang Fan, Jiao Chen, Yang Long, Shi Tang, Chunxia Jiang, Yong Xu
    BioMed Research International.2019; 2019: 1.     CrossRef
  • Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice
    Sorim Choung, Kyong Hye Joung, Bo Ram You, Sang Ki Park, Hyun Jin Kim, Bon Jeong Ku
    PPAR Research.2018; 2018: 1.     CrossRef
  • VCE‐004.3, a cannabidiol aminoquinone derivative, prevents bleomycin‐induced skin fibrosis and inflammation through PPARγ‐ and CB2 receptor‐dependent pathways
    Carmen del Rio, Irene Cantarero, Belén Palomares, María Gómez‐Cañas, Javier Fernández‐Ruiz, Carolina Pavicic, Adela García‐Martín, Maria Luz Bellido, Rafaela Ortega‐Castro, Carlos Pérez‐Sánchez, Chary López‐Pedrera, Giovanni Appendino, Marco A Calzado, Ed
    British Journal of Pharmacology.2018; 175(19): 3813.     CrossRef
  • EHP-101, an oral formulation of the cannabidiol aminoquinone VCE-004.8, alleviates bleomycin-induced skin and lung fibrosis
    Adela García-Martín, Martín Garrido-Rodríguez, Carmen Navarrete, Carmen del Río, María L. Bellido, Giovanni Appendino, Marco A. Calzado, Eduardo Muñoz
    Biochemical Pharmacology.2018; 157: 304.     CrossRef
  • Effects of Lobeglitazone, a New Thiazolidinedione, on Osteoblastogenesis and Bone Mineral Density in Mice
    Kyoung Min Kim, Hyun-Jin Jin, Seo Yeon Lee, Hyo Jin Maeng, Gha Young Lee, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Soo Lim
    Endocrinology and Metabolism.2017; 32(3): 389.     CrossRef
  • Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks
    Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi
    Diabetes & Metabolism Journal.2017; 41(5): 377.     CrossRef
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