{"title":"Erratum to “PTH-dependent stabilization of RANKL mRNA is associated with increased phosphorylation of the KH-type splicing regulatory protein” [Mol. Cell. Endocrinol. 595 (2025) 112412]","authors":"Gang-Qing Yao, Meiling Zhu, Karl Insogna","doi":"10.1016/j.mce.2025.112469","DOIUrl":"10.1016/j.mce.2025.112469","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112469"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boglárka Ágnes Vinnai , Rini Arianti , Pamela Fischer-Posovszky , Martin Wabitsch , László Fésüs , Endre Kristóf
{"title":"The importance of thiamine availability in the thermogenic competency of human adipocytes","authors":"Boglárka Ágnes Vinnai , Rini Arianti , Pamela Fischer-Posovszky , Martin Wabitsch , László Fésüs , Endre Kristóf","doi":"10.1016/j.mce.2025.112483","DOIUrl":"10.1016/j.mce.2025.112483","url":null,"abstract":"<div><div>Brown and beige adipocytes express uncoupling protein 1 (UCP1), which is located in the inner mitochondrial membrane and facilitates the dissipation of excess energy as heat. The activation of thermogenic adipocytes is a potential therapeutic target for treating type 2 diabetes mellitus, obesity, and related co-morbidities. Therefore, identifying novel approaches to stimulate the function of these adipocytes is crucial for advancing therapeutic strategies. Currently, there are limited amount of human adipocyte cell line models available to study the regulatory mechanisms of browning and key players in thermogenesis. The Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell line has been proven as a valuable model to investigate human adipocyte biology. In this study, we investigated how excess thiamine (vitamin B1), and the inhibition of thiamine transporters affect the expression of thermogenic markers and functional parameters during adrenergic stimulation in SGBS adipocytes. We found that limiting thiamine availability by pharmacological inhibitors impeded the dibutyryl-cAMP (db-cAMP)-dependent induction of thiamine transporter 1 and 2 (encoded by <em>SLC19A2</em> and <em>SLC19A3</em>), UCP1, PGC1a, and other browning markers, as well as proton leak respiration which is associated with UCP1-dependent heat generation. Contrarily, excess thiamine enhanced the db-cAMP-dependent induction of thiamine transporters, while UCP1, PGC1a, and other browning markers were upregulated. In addition, abundant amounts of thiamine increased the basal, unstimulated coupled and uncoupled respiration, and the expression of mitochondrial complex subunits. Our study highlights the critical role of excess thiamine in the thermogenic activation of SGBS adipocytes and its potential to enhance thermogenesis.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112483"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Wang , Mei Ji , Pusheng Yang , Jiaxin Zhang, Xiaotong Peng, Yaxin Miao, Wenwen Liu, Jing Sun
{"title":"Cyclooxygenase 2 overexpression suppresses Smad3 and augments ERK1/2 signaling activated by TGFβ1 in endometrial stromal cells: A novel insight into endometriosis pathogenesis","authors":"Tao Wang , Mei Ji , Pusheng Yang , Jiaxin Zhang, Xiaotong Peng, Yaxin Miao, Wenwen Liu, Jing Sun","doi":"10.1016/j.mce.2025.112470","DOIUrl":"10.1016/j.mce.2025.112470","url":null,"abstract":"<div><h3>Research question</h3><div>To investigate the underlying mechanisms driving the opposing effects of transforming growth factor-beta 1 (TGFβ1) on the proliferation of control (CESCs) and ectopic (EESCs) endometrial stromal cells.</div></div><div><h3>Design</h3><div>Cell proliferation assays (CCK-8 and colony formation) were employed to assess the effects of TGFβ1 on CESC and EESC proliferation. An immortalized human endometrial stromal cell line (HESC) was used to elucidate the mechanisms behind cytostatic effect of TGFβ1 and the potential role of cyclooxygenase (COX)-2 in mediating the modulation of TGFβ1 signaling.</div></div><div><h3>Results</h3><div>This study demonstrated that TGFβ1 inhibited the proliferation of CESCs and HESCs while significantly promoting the proliferation of EESCs. In both CESCs and HESCs, TGFβ1-induced growth arrest was primarily mediated by cell cycle arrest rather than apoptosis. Mechanistically, TGFβ1 activated both Smad3 and ERK1/2 signaling pathways, with Smad3 acting to inhibit proliferation and ERK1/2 to promote it. Notably, overexpression of COX-2 in HESCs abolished the cytostatic effect of TGFβ1 by enhancing ERK1/2 signaling and decreasing Smad3 protein levels and its nuclear translocation. Similar effects were observed following prostaglandin E2 (PGE2) treatment. In contrast, inhibition of COX-2 activity in EESCs resulted in increased Smad3 expression, reduced ERK1/2 activation, and a restoration of the cytostatic effect of TGFβ1.</div></div><div><h3>Conclusion</h3><div>COX-2 modulates the effects of TGFβ1 on endometrial stromal cells by altering the balance between the Smad3 and ERK1/2 signaling pathways, thereby converting TGFβ1 from a growth inhibitor to a proliferation stimulator.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112470"},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jalal Taneera , Deema Yaseen , Mona Youssef , Anila Khalique , Ola Saed Al Shehadat , Abdul Khader Mohammed , Yasser Bustanji , Mohamed I. Madkour , Waseem El-Huneidi
{"title":"Vitamin D augments insulin secretion via calcium influx and upregulation of voltage calcium channels: Findings from INS-1 cells and human islets","authors":"Jalal Taneera , Deema Yaseen , Mona Youssef , Anila Khalique , Ola Saed Al Shehadat , Abdul Khader Mohammed , Yasser Bustanji , Mohamed I. Madkour , Waseem El-Huneidi","doi":"10.1016/j.mce.2025.112472","DOIUrl":"10.1016/j.mce.2025.112472","url":null,"abstract":"<div><div>Vitamin D (VD) has been implicated in regulating insulin secretion and pancreatic β-cell function. Yet, the underlying molecular mechanism of VD in glucose homeostasis is not fully understood. This study investigates the effect of VD in regulating insulin secretion and pancreatic β-cell function. INS-1 β-cells were treated with VD to assess cell viability, reactive oxygen species production (ROS), insulin secretion, glucose uptake, proliferation, gene expression alterations, mitochondria metabolism, calcium influx, as well as the effects of antidiabetic drugs on <em>VDR</em> expression. Additionally, RNA sequencing from human pancreatic islets were utilized to examine <em>VDR</em> expression in relation to clinical parameters such as HbA1c, BMI, age, and gender.</div><div>VD treatment enhanced glucose-stimulated insulin secretion and elevated intracellular calcium levels without affecting insulin content, glucose uptake, ROS production, proliferation, or mitochondrial metabolism. Expression levels of key β-cell function genes, including <em>Ins</em>, <em>Pdx1</em>, and <em>Glut2,</em> remained unchanged with VD treatment. However, genes associated with calcium channels were upregulated. Cell exposure to rosiglitazone and dexamethasone elevated <em>VDR</em> expression in INS-1 cells, while metformin and insulin had no effect. RNA-seq analysis in human islets showed that <em>VDR</em> expression levels in human islets were significantly higher than in other metabolic tissues and were notably reduced in hyperglycemic donors compared to normoglycemic individuals. Furthermore, <em>VDR</em> expression positively correlated with several genes regulating voltage-gated calcium channels.</div><div>In conclusion, the study indicates that VD plays a significant role in enhancing insulin secretion through modulation of intracellular calcium dynamics, highlighting its potential therapeutic implications for managing type 2 diabetes.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112472"},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zaher Merhi , Michelle Goldsammler , Maureen J. Charron , Erkan Buyuk
{"title":"Dietary advanced glycation end products (AGEs) and superovulation with gonadotropins alter RAGE expression in the ovaries differently at each follicular stage of development","authors":"Zaher Merhi , Michelle Goldsammler , Maureen J. Charron , Erkan Buyuk","doi":"10.1016/j.mce.2025.112482","DOIUrl":"10.1016/j.mce.2025.112482","url":null,"abstract":"<div><div>The purpose of this study was to examine the deposition of advanced glycation end products (AGEs) and their receptors, RAGE, in ovarian follicles during folliculogenesis in mice fed high (H-AGE) or low (L-AGE) AGE diets and following superovulation with gonadotropins. We hypothesize that H-AGE diet is associated with increased AGE deposition and RAGE expression in various stages of ovarian follicular development, and superovulation with gonadotropins may alter these changes. C57BL/6J mice were fed low L-AGE (n = 10) or H-AGE (n = 10) diet for 12 weeks. In each group, half of each cohort (n = 5) were sacrificed at the end of 12 weeks while the other half (n = 5) were superovulated prior to sacrifice. Immunofluorescence staining of ovarian sections was used to determine AGE deposition and RAGE expression in ovarian follicles in a semi-quantitative manner. In all mice, AGE deposition and RAGE expression were observed in granulosa but not theca cells. In all mice, AGE deposition intensity increased as the follicles progressed through developmental stages from primordial to primary to secondary to prenatral/antral but then significantly dropped in the corpus luteum stage. RAGE staining was highly expressed equally in all stages of pre-ovulatory follicles but then significantly dropped in the corpus luteum post-ovulatory stage. Compared to mice on L-AGE diet, mice on H-AGE mice had significantly lower AGE deposition in their primordial follicles and lower RAGE intensity in their antral follicles. Following superovulation, mice in both groups had significantly lower AGE deposition and significantly lower RAGE expression but the drop in AGE deposition following superovulation was more pronounced in the H-AGE diet group compared to the L-AGE diet group in both pre-ovulatory and post-ovulatory follicles. Ovarian AGE deposition and RAGE expression changes differently during the natural follicular development. Opposite to expectations, the intake of diet rich in AGEs caused lower expression of the proinflammatroy RAGE, an effect that was more pronounced after gonadotropin exposure.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112482"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiyuan Dong , Liping He , Jinyi Wu , Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li
{"title":"Bisphenol A-induced cancer-associated adipocytes promotes breast carcinogenesis via CXCL12/AKT signaling","authors":"Zhiyuan Dong , Liping He , Jinyi Wu , Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li","doi":"10.1016/j.mce.2025.112473","DOIUrl":"10.1016/j.mce.2025.112473","url":null,"abstract":"<div><div>Bisphenol A (BPA), a commonly used plastic additive, is believed to cause obesity. As an environmental endocrine disruptor, BPA is closely associated with the onset and progression of BC. However, the molecular mechanisms underlying the promotion of breast cancer by BPA remain unclear. As obesity is a significant risk factor for breast cancer, this study aimed at exploring whether BPA facilitates the progression of breast cancer by inducing obesity. Using the National Health and Nutrition Examination Survey data, a positive correlation was observed between BPA exposure and the risk of sex-specific cancers among US adults with body mass index ≥30, suggesting that obesity may be influenced by urinary BPA. 3T3-L1 cells differentiated into mature adipocytes following treatment with 10<sup>−8</sup> M BPA, and subsequent treatment with 4T1-conditioned medium acquired properties associated with cancer-associated adipocytes (CAAs). Network pharmacology suggested that CXCL12 may serve as a key target gene in breast cancer progression. Follow-up PCR analysis revealed high CXCL12 expression in BPA-induced CAAs. Overexpression of CXCL12 promoted epithelial-mesenchymal transition (EMT) and 4T1 cell migration by activating the AKT pathway. <em>In vivo</em>, BPA-induced CAAs accelerated tumor growth compared to a controls xenografted with only 4T1 cells. In tissues from the BPA-CAAs group, the expression of CXCL12, markers associated with CAAs, phosphorylated AKT, N-cadherin, and vimentin was markedly elevated, whereas the expression of E-cadherin was reduced. In conclusion, BPA may induce adipose cells to differentiate into CAA-like cells and subsequently advance breast cancer EMT through the CXCL12/AKT pathway.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112473"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaohan Yu , Xinyan Pan , Mei Huang , Xiaoye Lin , Xiaohui Wang
{"title":"Chemerin mediates exercise-induced improvements of bone microstructure and bone mass in diabetes or high fat diet mice","authors":"Xiaohan Yu , Xinyan Pan , Mei Huang , Xiaoye Lin , Xiaohui Wang","doi":"10.1016/j.mce.2025.112471","DOIUrl":"10.1016/j.mce.2025.112471","url":null,"abstract":"<div><div>To clarify the roles and mechanisms of adipokine chemerin in exercise-induced bone improvements in type 2 diabetes mellitus (DM) mice and mice fed on high fat diet (HFD). DM mice were established by HFD + streptozotocin injection, exogenous chemerin was supplemented prior to running, and found that exogenous chemerin reversed 6-week exercise-induced improvements in cancellous bone parameters in DM mice. While adipose-specific chemerin knockout improved microstructure and mass of cancellous bone in HFD mice and further increased exercise-induced bone improvements, accompanied with promoted osteogenesis and inhibited osteoclasis represented as the changes of RANKL, M-CSF, Runx2, Osterix, OPG, ALP and CTSK. These results indicated that reduced chemerin contributed to exercise-induced enhancements in the microstructure and mass of cancellous bone in DM and HFD mice in association with osteogenesis promotion and osteoclasis inhibition, which is beneficial to clarify chemerin's impact on bone remodeling in metabolic diseases at sedentary and exercise states.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112471"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glaecir Roseni Mundstock Dias , Andrea Claudia Freitas Ferreira , Leandro Miranda-Alves , Jones Bernardes Graceli , Denise Pires de Carvalho
{"title":"Endocrine Disruptors Chemicals: Impacts of Bisphenol A, Tributyltin and Lead on Thyroid Function","authors":"Glaecir Roseni Mundstock Dias , Andrea Claudia Freitas Ferreira , Leandro Miranda-Alves , Jones Bernardes Graceli , Denise Pires de Carvalho","doi":"10.1016/j.mce.2025.112467","DOIUrl":"10.1016/j.mce.2025.112467","url":null,"abstract":"<div><div>The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate. Thus, compounds able to affect THs synthesis, transport, and action could produce important deleterious effects, impacting the development of metabolic and endocrine diseases. Herein, we will review the main effects of EDCs on the thyroid axis, with special emphasis on the widely used substances bisphenol A (BPA), employed in the synthesis of polycarbonate plastics and epoxy resins; tributyltin (TBT), an organotin chemical substance widely used in several agro-industrial applications; and lead (Pb), a ubiquitous environmental and occupational polluting heavy metal. Exposure to these EDCs occurs mainly from the ingestion of contaminated food and beverages. Furthermore, there are few epidemiological studies evaluating human risk, and experimental studies employ different exposure models, making it difficult to integrate results. However, even low doses of these EDCs warn of thyrotoxicity. Since THs homeostasis is essential for health and humans are increasingly being exposed to EDCs, it is important to clarify which substances might act as thyroid hormone system disrupting chemicals and how they act in order to try to overcome their deleterious effects and limit the exposure to these compounds.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112467"},"PeriodicalIF":3.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Lin , Yikai Shen , Yiwen Xia , Ying Li , Tianlu Jiang , Xusheng Shen , Yiwang Fu , Diancai Zhang , Li Yang , Hao Xu , Zekuan Xu , Linjun Wang
{"title":"Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice","authors":"Jie Lin , Yikai Shen , Yiwen Xia , Ying Li , Tianlu Jiang , Xusheng Shen , Yiwang Fu , Diancai Zhang , Li Yang , Hao Xu , Zekuan Xu , Linjun Wang","doi":"10.1016/j.mce.2025.112464","DOIUrl":"10.1016/j.mce.2025.112464","url":null,"abstract":"<div><h3>Objective</h3><div>The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.</div></div><div><h3>Methods</h3><div>We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (<em>GCG</em>), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.</div></div><div><h3>Conclusions</h3><div>ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112464"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bingjie Wang , Jinghuai Ni , Lingling Yu , Shuai Chen , Wenbin Shang , Penghua Fang , Wen Min
{"title":"Loss of chemerin prevents ovariectomy-induced osteoporosis in mice through intraosseous vascular remodeling","authors":"Bingjie Wang , Jinghuai Ni , Lingling Yu , Shuai Chen , Wenbin Shang , Penghua Fang , Wen Min","doi":"10.1016/j.mce.2025.112465","DOIUrl":"10.1016/j.mce.2025.112465","url":null,"abstract":"<div><div>Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2<sup>−/−</sup>) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2<sup>−/−</sup> mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2<sup>−/−</sup> mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2<sup>−/−</sup> mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2<sup>−/−</sup> mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2<sup>−/−</sup> mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112465"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}