ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.

Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification.

ACVR1 extends inflammatory responses in human induced pluripotent stem cell-derived macrophages.

Macrophages play crucial roles in many human disease processes. However, obtaining large numbers of primary cells for study is often difficult. We describe 2D and 3D methods for directing human induced pluripotent stem cells (hiPSCs) into macrophages (iMACs).

NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification.

Background: Inflammation helps regulate normal growth and tissue repair. Although bone morphogenetic proteins (BMPs) and inflammation are known contributors to abnormal bone formation, how these pathways interact in ossification remains unclear.

Methods: We examined this potential link in patients with fibrodysplasia ossificans progressiva (FOP), a genetic condition of progressive heterotopic ossification caused by activating mutations in the Activin A type I receptor (ACVR1/ALK2).

Modeling Smith-Lemli-Opitz syndrome with induced pluripotent stem cells reveals a causal role for Wnt/β-catenin defects in neuronal cholesterol synthesis phenotypes.

Smith-Lemli-Opitz syndrome (SLOS) is a malformation disorder caused by mutations in DHCR7, which impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. SLOS results in cognitive impairment, behavioral abnormalities and nervous system defects, though neither affected cell types nor impaired signaling pathways are fully understood. Whether 7DHC accumulation or cholesterol loss is primarily responsible for disease pathogenesis is also unclear.

Selective suppression of endothelial cytokine production by progesterone receptor.

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide.