Ablation of Rassf2 induces bone defects and subsequent haematopoietic anomalies in mice

Title
Ablation of Rassf2 induces bone defects and subsequent haematopoietic anomalies in mice
Author(s)
정대원송후근[송후근]김현수이경희이다혜[이다혜]김태신[김태신]송지연[송지연]이동준[이동준]최동욱[최동욱]고창용[고창용]김한성[김한성]신홍인[신홍인]최주현[최주현]박희동[박희동]박찬규[박찬규]임대식[임대식]
Keywords
STEM-CELL NICHE; HIPPO SIGNALING PATHWAY; TUMOR-SUPPRESSOR; ORGAN SIZE; KAPPA-B; SELECTIVE-INHIBITION; PROGENITOR CELLS; IN-VIVO; OSTEOCLAST; CANCER
Issue Date
201203
Publisher
NATURE PUBLISHING GROUP
Citation
EMBO JOURNAL, v.31, no.5, pp.1147 - 1159
Abstract
RASSF2 belongs to the Ras-association domain family (RASSF) of proteins, which may be involved in the Hippo signalling pathway. However, the role of RASSF2 in vivo is unknown. Here, we show that Rassf2 knockout mice manifest a multisystemic phenotype including haematopoietic anomalies and defects in bone remodelling. Bone marrow (BM) transplantation showed that Rassf2(-/-) BM cells had a normal haematopoietic reconstitution activity, indicating no intrinsic haematopoietic defects. Notably, in vitro differentiation studies revealed that ablation of Rassf2 suppressed osteoblastogenesis but promoted osteoclastogenesis. Co-culture experiments showed that an intrinsic defect in osteoblast differentiation from Rassf2(-/-) osteoblast precursors likely leads to both haematopoiesis and osteoclast defects in Rassf2(-/-) mice. Moreover, Rassf2 deficiency resulted in hyperactivation of nuclear factor (NF)-kappa B during both osteoclast and osteoblast differentiation. RASSF2 associated with I kappa B kinase (IKK) alpha and beta forms, and suppressed IKK activity. Introduction of either RASSF2 or a dominant-negative form of IKK into Rassf2(-/-) osteoclast or osteoblast precursors inhibited NF-kappa B hyperactivation and normalized osteoclast and osteoblast differentiation. These observations indicate that RASSF2 regulates osteoblast and osteoclast differentiation by inhibiting NF-kappa B signalling. The EMBO Journal (2012) 31, 1147-1159. doi: 10.1038/emboj.2011.480; Published online 6 January 2012
URI
http://hdl.handle.net/YU.REPOSITORY/29605http://dx.doi.org/10.1038/emboj.2011.480
ISSN
0261-4189
Appears in Collections:
의과대학 > 미생물학교실 > Articles
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