Osteoblasts from a Mandibuloacral dysplasia patient induce human blood precursors to differentiate into active osteoclasts

Mandibuloacral dysplasia type A (MADA) is a rare disease caused by mutations in the LMNA gene encoding A type lamins. Patients affected by MADA suffer from partial lipodystrophy, skin abnormalities and accelerated aging. Typical of MADA is also bone resorption at defined districts including terminal phalanges, mandible and clavicles. Little is known about the biological mechanism underlying osteolysis in MADA. In the reported study, we analyzed an osteoblast primary culture derived from the cervical vertebrae of a MADA patient bearing the homozygous R527H LMNA mutation. MADA osteoblasts showed nuclear abnormalities typical of laminopathic cells, but they proliferated in culture and underwent differentiation upon stimulation with dexametasone and beta-glycerophosphate. Differentiated osteoblasts showed proper production of bone mineral matrix until passage 8 in culture, suggesting a good differentiation activity.