Effect of Chordin-Like 1 on MC3T3-E1 and Human Mesenchymal Stem Cells

Fernandes, Hugo; Dechering, Koen J.; Someren, Eugene van; Steeghs, Ilse; Apotheker, Marion; Mentink, Anouk; Blitterswijk, Clemens A. van; Boer, Jan de

doi:10.1159/000281825

Cited by 12 publications

(9 citation statements)

References 93 publications

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“…We show that CHDL1 alone, or even in combination with TSG, does not modify proliferation, at difference of studies in other systems [53]. The effect of NOGGIN and both CHDL-1 and CHDL-2 on cultures of digit progenitors, concerns tissue differentiation, and becomes intensely potentiated by TSG.…”

Section: Discussionmentioning

confidence: 69%

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Expression and Functional Study of Extracellular BMP Antagonists during the Morphogenesis of the Digits and Their Associated Connective Tissues

et al. 2013

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The purpose of this study is to gain insight into the role of BMP signaling in the diversification of the embryonic limb mesodermal progenitors destined to form cartilage, joints, and tendons. Given the importance of extracellular BMP modulators in in vivo systems, we performed a systematic search of those expressed in the developing autopod during the formation of the digits. Here, we monitored the expression of extracellular BMP modulators including: Noggin, Chordin, Chordin-like 1, Chordin-like 2, Twisted gastrulation, Dan, BMPER, Sost, Sostdc1, Follistatin, Follistatin-like 1, Follistatin-like 5 and Tolloid. These factors show differential expression domains in cartilage, joints and tendons. Furthermore, they are induced in specific temporal patterns during the formation of an ectopic extra digit, preceding the appearance of changes that are identifiable by conventional histology. The analysis of gene regulation, cell proliferation and cell death that are induced by these factors in high density cultures of digit progenitors provides evidence of functional specialization in the control of mesodermal differentiation but not in cell proliferation or apoptosis. We further show that the expression of these factors is differentially controlled by the distinct signaling pathways acting in the developing limb at the stages covered by this study. In addition, our results provide evidence suggesting that TWISTED GASTRULATION cooperates with CHORDINS, BMPER, and NOGGIN in the establishment of tendons or cartilage in a fashion that is dependent on the presence or absence of TOLLOID.

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Section: Discussionmentioning

confidence: 69%

“…The low anti-BMP influence on gene regulation in rh-CHDL-1 alone treatments prompted us to check whether it has an effect promoting cell proliferation as reported in cultures of human mesenchymal stem cells [53]. However, no changes in cell proliferation or apoptosis were observed in cultures treated with different doses of CHDL-1 (Fig.…”

Section: Resultsmentioning

confidence: 83%

Expression and Functional Study of Extracellular BMP Antagonists during the Morphogenesis of the Digits and Their Associated Connective Tissues

et al. 2013

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“…Previous studies demonstrated that CHRDL1 enhanced the proliferation of MSCs [62]. IGSF10 was a unique marker of early osteochondral progenitor cells [63] and TWIST2 played a role to maintain MSCs in preosteoblast-like state [64, 65].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

et al. 2014

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Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA) and 20%–39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

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“…Follistatin is secreted by adipose tissue explants (27), and noggin is a well-established and secreted inhibitor that binds to the BMP receptors, but its biological functions are mostly undetermined (6,28). Chordin and chordin-like-1 (CHRDL1) are secreted proteins that bind BMP2, -4, and -7 (29,30), and CHRDL1 and has been shown to enhance the proliferation of human mesenchymal stem cells (31). Gremlin-1 (GREM1) is a potent extra-and intracellular inhibitor of BMP4 (32) and is involved in fibrosis and arthritis development (33).…”

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confidence: 99%

BMP4 and BMP Antagonists Regulate Human White and Beige Adipogenesis

et al. 2015

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The limited expandability of subcutaneous adipose tissue, due to reduced ability to recruit and differentiate new adipocytes, prevents its buffering effect in obesity and is characterized by expanded adipocytes (hypertrophic obesity). Bone morphogenetic protein-4 (BMP4) plays a key role in regulating adipogenic precursor cell commitment and differentiation. We found BMP4 to be induced and secreted by differentiated (pre)adipocytes, and BMP4 was increased in large adipose cells. However, the precursor cells exhibited a resistance to BMP4 owing to increased secretion of the BMP inhibitor Gremlin-1 (GREM1). GREM1 is secreted by (pre)adipocytes and is an inhibitor of both BMP4 and BMP7. BMP4 alone, and/or silencing GREM1, increased transcriptional activation of peroxisome proliferator–activated receptor γ and promoted the preadipocytes to assume an oxidative beige/brown adipose phenotype including markers of increased mitochondria and PGC1α. Driving white adipose differentiation inhibited the beige/brown markers, suggesting the presence of multipotent adipogenic precursor cells. However, silencing GREM1 and/or adding BMP4 during white adipogenic differentiation reactivated beige/brown markers, suggesting that increased BMP4 preferentially regulates the beige/brown phenotype. Thus, BMP4, secreted by white adipose cells, is an integral feedback regulator of both white and beige adipogenic commitment and differentiation, and resistance to BMP4 by GREM1 characterizes hypertrophic obesity.

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Effect of Chordin-Like 1 on MC3T3-E1 and Human Mesenchymal Stem Cells

Cited by 12 publications

References 93 publications

Expression and Functional Study of Extracellular BMP Antagonists during the Morphogenesis of the Digits and Their Associated Connective Tissues

Expression and Functional Study of Extracellular BMP Antagonists during the Morphogenesis of the Digits and Their Associated Connective Tissues

Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

BMP4 and BMP Antagonists Regulate Human White and Beige Adipogenesis

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