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Bone morphogenetic proteins (BMPs) play a critical role in the growth and steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types. The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs. A strategy of RNA interference (RNAi)-mediated 'gene silencing' of Smad4, a core molecule mediating the intracellular BMP/Smad signal transduction pathways, was used to interrupt endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited growth, and induced apoptosis of porcine GCs, while decreasing estradiol production. In addition, interrupted BMP/Smad signaling significantly (P<0.05) changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.
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http://dx.doi.org/10.1631/jzus.B1000079 | DOI Listing |
Am J Hematol
September 2025
Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. We have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo. Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis.
View Article and Find Full Text PDFOsteoporos Sarcopenia
June 2025
School of Medicine, Hallym University, Chuncheon, South Korea.
SP7, also known as Osterix, is a zinc finger-containing transcription factor, plays a crucial role in osteoblast differentiation and bone formation. This review examines the molecular mechanisms underlying SP7's regulatory functions, highlighting its interactions with key signaling pathways such as BMP-SMAD, Wnt/β-catenin, and HIF-1α. SP7 acts downstream of RUNX2 to regulate osteogenic gene expression, including collagen Type I Alpha 1 (COL1A1), alkaline phosphatase (ALP) and osteocalcin (OCN).
View Article and Find Full Text PDFFront Cell Dev Biol
July 2025
Xinjiang Key Laboratory of Mental Development and Learning Science, School of Psychology, Xinjiang Normal University, Urumqi, Xinjiang, China.
BMPR1B, a type I receptor in the BMP/Smad signaling pathway, was the first major gene identified in sheep () to regulate key reproductive traits such as ovulation rate (OR) and litter size (LS). Despite its critical role in reproductive performance, the transcriptional regulatory mechanisms governing ovine BMPR1B expression remain poorly understood. This study identified the promoter region of the BMPR1B gene and revealed that transcription factor ELK1 regulates its transcriptional activity.
View Article and Find Full Text PDFAdv Exp Med Biol
July 2025
Center for Translational Biomedical Iron Research, Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Heidelberg, Germany.
Disorders of iron metabolism pose a global health challenge. Over the past two decades, novel regulators of systemic iron homeostasis have been identified that can be manipulated for therapeutic purposes. In this context, inbred and genetically modified mice have proven to be valuable tools enabling precise investigation of gene functions and testing of new pharmacological treatments that in some cases have reached the clinical stage.
View Article and Find Full Text PDFZhongguo Gu Shang
June 2025
Department of Orthopaedics, Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou 311201, Zhejiang, China.
The healing of the tendon-bone interface is a complex dynamic process involving the interaction of multiple cellular and molecular signaling pathways. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into various types of cells, including osteoblasts, chondrocytes and adipocytes, etc., and have the potential to regenerate damaged tissues.
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