PPARG in osteocytes controls sclerostin expression, bone mass, marrow adiposity and mediates TZD-induced bone loss

Baroi, Sudipta; Czernik, Piotr J.; Chougule, Amit; Griffin, Patrick R.; Lecka‐Czernik, Beata

doi:10.1016/j.bone.2021.115913

Cited by 30 publications

(34 citation statements)

References 53 publications

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“…Recently, the tight link between energy metabolism and bone mass has been proved by increasing number of studies ( 33 , 34 ), PPARγ, as a key target regulating the metabolic network, was also been focused on. Studies have revealed that the mouse with osteocyte-specific PPARγ deletion showed an increased bone mass and a reduced bone marrow adiposity, which indicated PPARγ has a negative effect on bone quality ( 35 ). Our results of the qRT-PCR analysis can also give compelling evidences: the mRNA expression level of PPARγ was significantly increased in the GIOP group vs the blank group, while after treating with TFDR, the level showed a significant decline.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation

Zhang

et al. 2022

Front. Endocrinol.

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BackgroundGlucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis caused by the protracted or a large dosage of glucocorticoids (GCs). Total flavonoids of Drynariae rhizoma (TFDR) have been widely used in treating postmenopausal osteoporosis (POP). However, their therapeutic effects and potential mechanism against GIOP have not been fully elucidated.MethodsUltra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESIQ-TOF-MS) experiments were performed for qualitative analysis. We performed hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis to detect the changes in bone microstructure. The changes in biochemical parameters in the serum samples were determined by performing an enzyme-linked immunosorbent assay (ELISA). The prediction results of network pharmacology were verified via quantitative real-time polymerase chain reaction (qRT-PCR) to elucidate the potential mechanism of TFDR against GIOP.ResultsA total of 191 ingredients were identified in vitro and 48 ingredients in vivo. In the in-vivo experiment, the levels of the serum total cholesterol (TC), the serum triglyceride (TG), Leptin (LEP), osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRACP) and type-I collagen carboxy-terminal peptide (CTX-1) in the TFDR group significantly changed compared with those in the GIOP group. Moreover, the TFDR group showed an improvement in bone mineral density and bone microstructure. Based on the results of network pharmacology analysis, 67 core targets were selected to construct the network and perform PPI analysis as well as biological enrichment analysis. Five of the targets with high “degree value” had differential gene expression between groups using qRT-PCR.ConclusionTFDR, which may play a crucial role between adipose metabolism and bone metabolism, may be a novel remedy for the prevention and clinical treatment of GIOP.

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Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation

Zhang

et al. 2022

Front. Endocrinol.

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“…IL-6 exerts dual effects on the differentiation of osteoblasts and osteoclasts ( Wang and He, 2020 ). Moreover, PPARG is essential for sclerostin production, which has been approved as a target for treating OP ( Baroi et al, 2021 ). Here, we identified these genes as the key targets for OP treatment by the OSTEOWONDER capsule.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Fan

Zhou

et al. 2022

Front. Genet.

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Background: Osteoporosis (OP) is a serious and common bone metabolic disease with bone mass loss and bone microarchitectural deterioration. The OSTEOWONDER capsule is clinically used to treat OP. However, the potential regulatory mechanism of the OSTEOWONDER capsule in treatment of OP remains largely unknown.Methods: The bioactive compounds of herbs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The speculative targets of OP were screened out based on GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The gene modules and hub genes of OP were identified using a weighted gene co-expression network analysis (WGCNA). Then, an herb-compound-target network was constructed based on the above analyses. The biological function of targets was subsequently investigated, and a protein–protein interaction (PPI) network was constructed to identify hub targets of OP. Finally, molecular docking was performed to explore the interaction between compounds and targets.Results: A total of 148 compounds of eight herbs and the corresponding 273 targets were identified based on the TCMSP database. A total of 4,929 targets of OP were obtained based on GeneCards, DisGeNET, and OMIM databases. In addition, six gene modules and 4,235 hub genes of OP were screened out based on WGCNA. Generally, an herb-compound-target network, including eight herbs, 84 compounds, and 58 targets, was constructed to investigate the therapeutic mechanism of the OSTEOWONDER capsule for OP. The biofunction analysis indicated 58 targets mainly associated with the bone metabolism, stimulation response, and immune response. EGFR, HIF1A, MAPK8, IL6, and PPARG were identified as the hub therapeutic targets in OP. Moreover, the interaction between EGFR, HIF1A, MAPK8, IL6, PPARG, and the corresponding compounds (quercetin and nobiletin) was analyzed using molecular docking.Conclusion: Our finding discovered the possible therapeutic mechanisms of the OSTEOWONDER capsule and supplied the potential therapeutic targets for OP.

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“…The first short talk reported the role of the novel adipokine adipsin and its ability to activate the immune complement system in BMAT expansion promoted by caloric restriction or thiazolidinedione treatment (16). The second short talk described the role of PPARg in osteocytes, showing that the sclerostin gene is regulated by PPARg and that osteocyte-specific conditional knockout mice have a high bone mass and low BMAT phenotype (17). The third and final short talk in this session examined the regulatory role of the immune system complement factor H in bone and BMAT homeostasis (18).…”

Section: Session Iii: Endocrine Regulation Of Bone Marrow Adipose Tissue In Health and Diseasementioning

confidence: 99%

Report From the 6th International Meeting on Bone Marrow Adiposity (BMA2020)

2021

Self Cite

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The 6th International Meeting on Bone Marrow Adiposity (BMA) entitled “Marrow Adiposity: Bone, Aging, and Beyond” (BMA2020) was held virtually on September 9th and 10th, 2020. The mission of this meeting was to facilitate communication and collaboration among scientists from around the world who are interested in different aspects of bone marrow adiposity in health and disease. The BMA2020 meeting brought together 198 attendees from diverse research and clinical backgrounds spanning fields including bone biology, endocrinology, stem cell biology, metabolism, oncology, aging, and hematopoiesis. The congress featured an invited keynote address by Ormond MacDougald and ten invited speakers, in addition to 20 short talks, 35 posters, and several training and networking sessions. This report summarizes and highlights the scientific content of the meeting and the progress of the working groups of the BMA society (http://bma-society.org/).

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PPARG in osteocytes controls sclerostin expression, bone mass, marrow adiposity and mediates TZD-induced bone loss

Cited by 30 publications

References 53 publications

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Report From the 6th International Meeting on Bone Marrow Adiposity (BMA2020)

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