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Inhibiting Dickkopf-1 (Dkk1) Removes Suppression of Bone Formation and Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma. Vrije Universiteit Brussel

Deborah J Heath, Andrew Chantry, Clive H. Buckle, Les Coulton, John D. Shaughnessy, Jr, Holly R. Evans, John A. Snowden, David R. Stover, Karin Vanderkerken, Peter I. Croucher, et al.
Multiple myeloma (MM) is associated with the development of osteolytic bone disease, mediated by increased osteoclastic bone resorption and impaired osteoblastic bone formation. Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and correlates with osteolytic bone disease. In this study, we investigated the effect of inhibiting Dkk1, on the development of osteolytic ...

Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients : correlation with the Trabecular Bone Score (TBS) Ghent University

Barbara Ruaro, Andrea Casabella, Sabrina Paolino, Carmen Pizzorni, Massimo Ghio, Chiara Seriolo, Luigi Molfetta, Patrizio Odetti, Vanessa Smith, Maurizio Cutolo, et al.
The aim of this research was to determine any correlations between Dickkopf-1 serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any difference in Dkk-1 serum levels between SSc and RA patients and a control group (CNT) of healthy subjects. A prospective study was ...

Tenascin-C downregulates Wnt inhibitor Dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model Ghent University

Falk Saupe, Anja Schwenzer, Yundan Jia, Isabelle Gasser, Caroline Spenlé, Benoit Langlois, Martial Kammerer, Olivier Lefebvre, Ruslan Hlushchuk, Tristan Rupp, et al.
The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic beta-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance ...

Dickkopf-3 is regulated by the MYCN-induced miR-17-92 cluster in neuroblastoma Ghent University

Sara De Brouwer, Pieter Mestdagh, Irina Lambertz, Filip Pattyn, Anne De Paepe, Frank Westermann, Christina Schroeder, Johannes H Schulte, Alexander Schramm, Katleen De Preter, et al.
Neuroblastoma (NB) is a paediatric tumour with a remarkable diverse clinical behaviour. Approximately half of the high stage aggressive tumours are characterized by MYCN gene amplification but our understanding of the role of MYCN in NB oncogenesis is incomplete. Previous studies have shown that MYCN expression is inversely correlated with expression of Dickkopf-3 (DKK3), a gene encoding an extracellular protein with presumed tumour suppressor ...

The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage Vrije Universiteit Brussel Ghent University

Thiberiu Banica, Hans-Georg Zmierczak, Stefan Goemaere, Stefanie De Buyser, Tom Fiers, Jean-Marc Kaufman, Jean De Schepper, Bruno Lapauw

INTRODUCTION: This study investigates peri-pubertal changes in bone turnover markers, Wnt-signalling markers, insulin-like growth factor-1 (IGF-1) and sex steroid levels, and how they reflect skeletal development in peri-pubertal boys.

MATERIALS AND METHODS: Population-based study in 118 peri-pubertal boys from the NINIOS cohort (age range at baseline 5.1-17.3 years) with repeated measurements at baseline and after two years. Serum ...

Changes in bone formation regulator biomarkers in early axial spondyloarthritis KU Leuven

Rik Lories
OBJECTIVE: The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. METHODS: The DEvenir des Spondyloarthropathies ...

Effect of Gut Involvement in Patients with High Probability of Early Spondyloarthritis: Data from the DESIR Cohort KU Leuven

Rik Lories
OBJECTIVE: Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort. METHODS: DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and ...

T cell-based targeted immunotherapies for patients with multiple myeloma Vrije Universiteit Brussel

Lei Wang, Nan Jin, Anita Schmitt, Jochen Greiner, Georg Malcherek, Jiju Mani, Dirk Hose, Marc S Raab, Anthony D Ho

Despite high-dose chemotherapy followed by autologs stem-cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression-free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect ...

Immunomodulatory drugs thalidomide and lenalidomide affect osteoblast differentiation of human bone marrow stromal cells in vitro Vrije Universiteit Brussel

Arnold Bolomsky, Martin Schreder, Tobias Meißner, Dirk Hose, Heinz Ludwig, Sabine Pfeifer, Niklas Zojer

Osteoblastic activity is severely impaired in active myeloma, contributing to the development of myeloma bone disease. Although several drugs reducing osteoclast-mediated bone degradation are in clinical use, approaches to specifically augment bone formation are at an early stage of development. Novel antimyeloma drugs not only directly act on myeloma cells, but impact on the microenvironment as well. Proteasome inhibitors were previously ...