The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats
Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPAR...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556523002024 |
| _version_ | 1827815818925178880 |
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| author | Jingzheng Fan Dalong Zhang Yuyan Jiang Lechang Yu Bin Han Zhiyong Qian |
| author_facet | Jingzheng Fan Dalong Zhang Yuyan Jiang Lechang Yu Bin Han Zhiyong Qian |
| author_sort | Jingzheng Fan |
| collection | DOAJ |
| description | Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague–Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations. |
| first_indexed | 2024-03-12T00:06:05Z |
| format | Article |
| id | doaj.art-52bea29ff8be43f09edc1e0003fef95f |
| institution | Directory Open Access Journal |
| issn | 1873-6815 |
| language | English |
| last_indexed | 2024-03-12T00:06:05Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj.art-52bea29ff8be43f09edc1e0003fef95f2023-09-17T04:55:50ZengElsevierExperimental Gerontology1873-68152023-10-01181112281The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female ratsJingzheng Fan0Dalong Zhang1Yuyan Jiang2Lechang Yu3Bin Han4Zhiyong Qian5Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Corresponding author at: Department of Geriatrics, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, China.Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, ChinaDepartment of Nuclear medicine, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China; Corresponding author at: Department of Toxicology, Tianjin Centers for Disease Control and Prevention, 6 Huayue Rd, Tianjin 300011, China.Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague–Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations.http://www.sciencedirect.com/science/article/pii/S0531556523002024PPARγ antagonistGlucocorticoidAged female ratsBone marrow fatOsteoporosisMarrow adipogenesis |
| spellingShingle | Jingzheng Fan Dalong Zhang Yuyan Jiang Lechang Yu Bin Han Zhiyong Qian The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats Experimental Gerontology PPARγ antagonist Glucocorticoid Aged female rats Bone marrow fat Osteoporosis Marrow adipogenesis |
| title | The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats |
| title_full | The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats |
| title_fullStr | The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats |
| title_full_unstemmed | The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats |
| title_short | The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats |
| title_sort | effects of pparγ inhibitor on bones and bone marrow fat in aged glucocorticoid treated female rats |
| topic | PPARγ antagonist Glucocorticoid Aged female rats Bone marrow fat Osteoporosis Marrow adipogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S0531556523002024 |
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