Sharpin is a key regulator of skeletal homeostasis in a TNF-dependent manner
HW McGowan, JA Schuijers, BL Grills, SJ McDonald, JA Rickard, J Silke, AC McDonald
JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS | JMNI | Published : 2014
OBJECTIVES: SHARPIN is a subunit of LUBAC and regulates activation of NF-κB, a pivotal transcription factor in skeletal homeostasis. Mutated SHARPIN gene (cpdm) mice develop chronic proliferative dermatitis and systemic inflammation. Cpdm mice have an osteopaenic phenotype characterised by decreased cortical and trabecular bone volume, but whether this is a consequence of the hyper-inflammatory phenotype is unknown. The inflammatory phenotype of cpdm mice is prevented by Tnf deficiency so we examined cpdm.Tnf (-/-) mice to examine the role of SHARPIN in skeletal development. METHODS: This research determined the extent to which SHARPIN and TNF interact within the skeleton through analyses of..View full abstract
The authors would like to acknowledge the support from the Department of Human Biosciences, La Trobe University, in the award of a departmental grant. We thank Heinrich Korner for Tnf -/- mice. This work was supported by NHMRC grants (1025594, 1046984) and an NHMRC fellowship to JSilke (541901).