scholarly journals Control of Collagen Production in Mouse Chondrocytes by Using a Combination of Bone Morphogenetic Protein-2 and Small Interfering RNA Targeting Col1a1 for Hydrogel-Based Tissue-Engineered Cartilage

2013 ◽  
Vol 19 (8) ◽  
pp. 652-664 ◽  
Author(s):  
Emeline Perrier-Groult ◽  
Marielle Pasdeloup ◽  
Marilyne Malbouyres ◽  
Philippe Galéra ◽  
Frédéric Mallein-Gerin
Keyword(s):  
Bone Morphogenetic Protein ◽  
Small Interfering Rna ◽  
Bone Morphogenetic Protein 2 ◽  
Collagen Production ◽  
Morphogenetic Protein ◽  
Rna Targeting ◽  
Interfering Rna ◽  
Engineered Cartilage

scholarly journals BMP4 and BMP7 Suppress StAR and Progesterone Production via ALK3 and SMAD1/5/8-SMAD4 in Human Granulosa-Lutein Cells

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4269-4280 ◽  
Author(s):  
Han Zhang ◽  
Christian Klausen ◽  
Hua Zhu ◽  
Hsun-Ming Chang ◽  
Peter C. K. Leung
Keyword(s):  
Granulosa Cells ◽  
Small Interfering Rna ◽  
Regulatory Protein ◽  
Human Granulosa Cells ◽  
Progesterone Production ◽  
Morphogenetic Protein ◽  
Rna Targeting ◽  
Successful Establishment ◽  
Steroidogenic Acute Regulatory ◽  
Interfering Rna

Adequate production of progesterone by the corpus luteum is critical to the successful establishment of pregnancy. In animal models, bone morphogenetic protein (BMP) 4 and BMP7 have been shown to suppress either basal or gonadotropin-induced progesterone production, depending on the species examined. However, the effects of BMP4 and BMP7 on progesterone production in human granulosa cells are unknown. In the present study, we used immortalized (SVOG) and primary human granulosa-lutein cells to investigate the effects of BMP4 and BMP7 on steroidogenic acute regulatory protein (StAR) expression and progesterone production and to examine the underlying molecular mechanism. Treatment of primary and immortalized human granulosa cells with recombinant BMP4 or BMP7 decreased StAR expression and progesterone accumulation. In SVOG cells, the suppressive effects of BMP4 and BMP7 on StAR expression were blocked by pretreatment with inhibitors of activin receptor-like kinase (ALK)2/3/6 (dorsomorphin) or ALK2/3 (DMH1) but not ALK4/5/7 (SB-431542). Moreover, small interfering RNA-mediated depletion of ALK3, but not ALK2 or ALK6, reversed the effects of BMP4 and BMP7 on StAR expression. Likewise, BMP4- and BMP7-induced phosphorylation of SMAD 1/5/8 was reversed by treatment with DMH1 or small interfering RNA targeting ALK3. Knockdown of SMAD4, the essential common SMAD for BMP/TGF-β signaling, abolished the effects of BMP4 and BMP7 on StAR expression. Our results suggest that BMP4 and BMP7 down-regulate StAR and progesterone production via ALK3 and SMAD1/5/8-SMAD4 signaling in human granulosa-lutein cells.

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