![]() Hemophilia A and B are X-linked congenital bleeding disorders characterized by reduced or absent levels of coagulation factors VIII or IX, respectively. The review also raises unanswered questions, highlights the need for consolidated research efforts, and delineates future directions expected to advance this technology and optimize its use in this patient population. This review summarizes currently available data on the emerging role of this new imaging modality, its limitations, and gaps in knowledge. Musculoskeletal ultrasound-particularly, point-of-care musculoskeletal ultrasound-has emerged as a promising imaging modality for the early detection and management of hemophilic arthropathy, and for the evaluation of hemarthrosis and painful musculoskeletal episodes in patients with hemophilia. Hemophilic arthropathy assessment is a continually evolving process and is particularly challenging in children and young adults in whom joint disease may be missed or underestimated as obtaining serial “baseline” magnetic resonance imaging scans of multiple clinically asymptomatic or nearly asymptomatic joints may be unjustifiable and cost-ineffective. It results from repeated bleeding episodes in the joint and is characterized by synovial hypertrophy and cartilage and bony destruction. These data provide new evidence that further strengthens the important nature of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation in mouse Leydig cells.Īn in-depth high-throughput transcriptomic analysis of COUP-TFII-depleted Leydig cells reveals novel gene pathways and networks regulated by this orphan nuclear receptor.Bleeding with resultant hemophilic arthropathy constitutes the largest cause of morbidity in patients with hemophilia. Finally, analysis of the Gsta3 and Inha gene promoters showed that at least two of the downregulated genes are potentially new direct targets for COUP-TFII. Downregulated genes included hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (Hsd3b1), cytochrome P450, family 11, subfamily a, polypeptide 1 (Cyp11a1), prolactin receptor (Prlr), nuclear receptor subfamily 0, group B, member 2 (Shp/Nr0b2), ferredoxin 1 (Fdx1), scavenger receptor class B, member 1 (Scarb1), inhibin alpha (Inha), and glutathione S-transferase, alpha 3 (Gsta3). We validated the microarray data for a subset of the modulated genes by RT-qPCR. Many of the differentially expressed genes are known to be involved in lipid biosynthesis, lipid metabolism, male gonad development, and steroidogenesis. We identified 262 differentially expressed genes in COUP-TFII-depleted MA-10 cells. To provide new information into the mechanism of action of COUP-TFII in Leydig cells, we performed microarray analyses of COUP-TFII-depleted MA-10 Leydig cells. Until now, only a handful of target genes have been identified for COUP-TFII in Leydig cells. Steroid production has also been shown to be diminished in COUP-TFII-depleted Leydig cells, indicating an important functional role in steroidogenesis. ![]() In the testis, COUP-TFII is expressed and plays a role in the differentiation of cells committed to give rise to fully functional steroidogenic adult Leydig cells. ![]() ![]() Chicken ovalbumin upstream promoter-transcription factors I (COUP-TFI/NR2F1) and COUP-TFII (NR2F2) belong to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. In males, Leydig cells are the main producers of testosterone and insulin-like 3 (INS元), two hormones essential for sex differentiation and reproductive functions.
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