Lamins and bone disorders: current understanding and perspectives
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Chiara Gargiuli1, Elisa Schena1,2, Elisabetta Mattioli1,2, Marta Columbaro2, Maria Rosaria D'Apice3, Giuseppe Novelli3, Tiziana Greggi4 and Giovanna Lattanzi1,2
1CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy
2Rizzoli Orthopaedic Institute, Laboratory of Cell Biology, Bologna, Italy
3Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Rome, Italy
4Rizzoli Orthopaedic Institute, Spine Deformity Department, Bologna, Italy
Giovanna Lattanzi, email: email@example.com
Chiara Gargiuli, email: firstname.lastname@example.org
Keywords: lamin A/C; LMNA-related congenital muscular dystrophy (L-CMD); hutchinson-gilford progeria syndrome (HGPS); mandibuloacral dysplasia (MADA, MADB); bone turnover
Received: October 11, 2017 Accepted: March 22, 2018 Published: April 27, 2018
Lamin A/C is a major constituent of the nuclear lamina implicated in a number of genetic diseases, collectively known as laminopathies. The most severe forms of laminopathies feature, among other symptoms, congenital scoliosis, osteoporosis, osteolysis or delayed cranial ossification.
Importantly, specific bone districts are typically affected in laminopathies. Spine is severely affected in LMNA-linked congenital muscular dystrophy. Mandible, terminal phalanges and clavicles undergo osteolytic processes in progeroid laminopathies and Restrictive Dermopathy, a lethal developmental laminopathy. This specificity suggests that lamin A/C regulates fine mechanisms of bone turnover, as supported by data showing that lamin A/C mutations activate non-canonical pathways of osteoclastogenesis, as the one dependent on TGF beta 2.
Here, we review current knowledge on laminopathies affecting bone and LMNA involvement in bone turnover and highlight lamin-dependent mechanisms causing bone disorders. This knowledge can be exploited to identify new therapeutic approaches not only for laminopathies, but also for other rare diseases featuring bone abnormalities.
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