SMOC2 inhibits calcification of osteoprogenitor and endothelial cells
Authors: Silvia Monteagudo
Tine Peeters
Rik Lories
Frank P Luyten
Fr√©d√©ric Cailotto
Przemko Tylzanowski
Journal: PLoS ONE (2018)
Discipline: Multidisciplinary
Keywords: Tissue calcification; SMOC2; osteogenic differentiation; mineralization; calcium-binding
Affiliations: Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Laboratory for Developmental and Stem Cell Biology, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland., Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium., UMR 7365 CNRS-Universit√© de Lorraine, Ing√©nierie Mol√©culaire et Physiopathologie Articulaire (IMoPA), Biop√¥le de l'Universit√© de Lorraine, Campus Biologie-Sant√©, Vandoeuvre Les Nancy, France.

Abstract:  Tissue calcification is an important physiological process required for the normal structure and function of bone. However, ectopic or excessive calcification contributes to diseases such as chondrocalcinosis, to calcium deposits in the skin or to vascular calcification. SMOC2 is a member of the BM-40/osteonectin family of calcium-binding secreted matricellular proteins. Using osteoprogenitor MC3T3-E1 cells stably overexpressing SMOC2, we show that SMOC2 inhibits osteogenic differentiation and extracellular matrix mineralization. Stable Smoc2 knockdown in these cells had no effect on mineralization suggesting that endogenous SMOC2 is not essential for the mineralization process. Mineralization in MC3T3-E1 cells overexpressing mutant SMOC2 lacking the extracellular calcium-binding domain was significantly increased compared to cells overexpressing full length SMOC2. When SMOC2 overexpressing cells were cultured in the presence of extracellular calcium supplementation, SMOC2's inhibitory effect on calcification was rescued. Our observations were translationally validated in primary human periosteal-derived cells. Furthermore, SMOC2 was able to impair mineralization in transdifferentiated human umbilical vein endothelial cells. Taken together, our data indicate that SMOC2 can act as an inhibitor of mineralization. We propose a possible role for SMOC2 to prevent calcification disorders. 

Retracted: No

PubPeer comments:
  Red box showing suspected image duplication. , 
 We regret the potential confusion about the identified images. We hereunder provide high magnifications from the PDF of the paper (with and without arrows indicating differences), high resolution magnifications of the original images as well as the orginal complete pictures of the experiment. The images that were flagged in the post represent a baseline condition in which the cells have not differentiated. Hence, the color reaction is absent, which makes it difficult to discriminate between different well of identically manufactured plates. High magnification from journal s PDF  High magnification from journal s PDF annotated  High resolution image from original files annotated  Original overview pictures of the plates  Row A represents 3 wells with SMOC2+ cells, Row E represents 3 wells with deltaCaBD cells. The images in the manuscript are from well A1 and well E1. , 
 #2 Thanks a lot for clarification. ,