HIV-1 protein induced modulation of primary human osteoblast differentiation and function via a Wnt/β-catenin-dependent mechanism.
AffiliationClinical Research Centre, UCD School of Medicine & Medical Science, Mater Misericordiae University Hospital, Dublin, Ireland; Department of Trauma & Orthopaedic Surgery, Royal College of Surgeons in Ireland, Cappagh National Orthopaedic Hospital, Dublin, Ireland. email@example.com.
MetadataShow full item record
CitationHIV-1 protein induced modulation of primary human osteoblast differentiation and function via a Wnt/β-catenin-dependent mechanism. 2013, 31 (2):218-26 J. Orthop. Res.
JournalJournal of orthopaedic research : official publication of the Orthopaedic Research Society
AbstractHIV infection is associated with metabolic bone disease resulting in bone demineralization and reduced bone mass. The molecular mechanisms driving this disease process have yet to be elucidated. Wnt/β-catenin signaling plays a key role in bone development and remodeling. We attempted to determine the effects of the HIV-1 protein, gp120, on Wnt/β-catenin signaling at an intracellular and transcriptional level in primary human osteoblasts (HOBs). This work, inclusive of experimental controls, was part of a greater project assessing the effects of a variety of different agents on Wnt/β-catenin signaling (BMC Musculoskelet Disord 2010;11:210).We examined the phenotypic effects of silencing and overexpressing the Wnt antagonist, Dickkopf-1 (Dkk1) in HOBs treated with gp120. HOBs exposed to gp120 displayed a significant reduction in alkaline phosphatase activity (ALP) activity and cell proliferation and increased cellular apoptosis over a 48 h time course. Immunocytochemistry demonstrated a significant reduction in intracytosolic and intranuclear β-catenin in response to HIV-1 protein exposure. These changes were associated with a reduction of TCF/LEF-mediated transcription, the transcriptional outcome of canonical Wnt β-catenin signaling. Silencing Dkk1 expression in HOBs exposed to gp120 resulted in increased ALP activity and cell proliferation, and decreased cellular apoptosis relative to scrambled control. Dkk1 overexpression exacerbated the inhibitory effect of gp120 on HOB function, with decreases in ALP activity and cell proliferation and increased cellular apoptosis relative to vector control. Wnt/β-catenin signaling plays a key regulatory role in HIV-associated bone loss, with Dkk1, aputative central mediator in this degenerative process. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 218-226, 2013.
- Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.
- Authors: Butler JS, Queally JM, Devitt BM, Murray DW, Doran PP, O'Byrne JM
- Issue date: 2010 Sep 15
- Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma.
- Authors: Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD Jr
- Issue date: 2008 Apr
- Differentiation-inducing factor-1 alters canonical Wnt signaling and suppresses alkaline phosphatase expression in osteoblast-like cell lines.
- Authors: Matsuzaki E, Takahashi-Yanaga F, Miwa Y, Hirata M, Watanabe Y, Sato N, Morimoto S, Hirofuji T, Maeda K, Sasaguri T
- Issue date: 2006 Aug
- FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signaling-dependent Runx2 expression.
- Authors: Hamidouche Z, Haÿ E, Vaudin P, Charbord P, Schüle R, Marie PJ, Fromigué O
- Issue date: 2008 Nov
- Inhibition of Wnt/β-catenin signaling by dexamethasone promotes adipocyte differentiation in mesenchymal progenitor cells, ROB-C26.
- Authors: Naito M, Omoteyama K, Mikami Y, Takahashi T, Takagi M
- Issue date: 2012 Dec