ldn-193189 and Blast-Injuries

Traumatic heterotopic ossification (tHO) commonly develops in wounded service members who sustain high-energy and blast-related traumatic amputations. Currently, no safe and effective preventive measures have been identified for this patient population. Bone morphogenetic protein (BMP) signaling blockade has previously been shown to reduce ectopic bone formation in genetic models of HO. In this study, we demonstrate the efficacy of small-molecule inhibition with LDN193189 (ALK2/ALK3 inhibition), LDN212854 (ALK2-biased inhibition), and BMP ligand trap ALK3-Fc at inhibiting early and late osteogenic differentiation of tissue-resident mesenchymal progenitor cells (MPCs) harvested from mice subjected to burn/tenotomy, a well-characterized trauma-induced model of HO. Using an established rat tHO model of blast-related extremity trauma and methicillin-resistant

Topics: Animals; Blast Injuries; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Proteins; Burns; Cell Differentiation; Disease Models, Animal; Humans; Immunoconjugates; Immunoglobulin Fc Fragments; Ligands; Lower Extremity; Male; Mesenchymal Stem Cells; Mice, Inbred C57BL; Ossification, Heterotopic; Osteogenesis; Pyrazoles; Pyrimidines; Rats, Sprague-Dawley; Signal Transduction; Wounds and Injuries; X-Ray Microtomography