Adamts17 is involved in skeletogenesis through modulation of BMP-Smad1/5/8 pathway

Oichi, Takeshi; Taniguchi, Yuki; Soma, Kazuhito; Oshima, Yasushi; Yano, Fumiko; Mori, Yoshifumi; Chijimatsu, Ryota; Kim‐Kaneyama, Joo‐ri; Tanaka, Sakae; Saito, Taku

doi:10.1007/s00018-019-03188-0

Cited by 30 publications

(34 citation statements)

References 38 publications

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“…The activation of the BMP pathway induces the phosphorylation of Smad1/5/8. Then, the phosphorylated Smad1/5/8 bind to Smad4 and move into the nucleus, thus activating downstream factors of the BMP pathway [37]. Additionally, the Wnt/β-catenin signalling is critical in the therapy of osteoporosis, since it has a signi cant impact on promoting osteogenesis and regulating bone metabolism [38].…”

Section: Discussionmentioning

confidence: 99%

Gentiopicroside promotes osteogenesis and prevents bone loss in ovariectomized mice by modulation of β-catenin-BMP2 signaling pathway

Jiang¹,

Zhong²,

Li³

et al. 2020

Preprint

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Background: Osteoporosis is characterized by increased bone fragility and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN) is widely used in the traditional Chinese medicine thanks to its multiple pharmacological activities including the suppression of osteoclastogenesis. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy.Methods: In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, while in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months.Results: Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and upregulated the osteogenic factors (Runx2, OSX, OCN, OPN, and BMP2). In vivo, GEN strengthened the secretion of Runx2, OCN, and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/β-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/β-catenin inhibitor DKK1. Silencing the β-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only β-catenin was silenced, while the knockout of BMP2 did not affect β-catenin expression induced by GEN. Interpretation.Conclusions: GEN promotes BMSC osteogenesis by regulating β-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Gentiopicroside promotes osteogenesis and prevents bone loss in ovariectomized mice by modulation of β-catenin-BMP2 signaling pathway

Jiang¹,

Zhong²,

Li³

et al. 2020

Preprint

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“…Phenotypes of knockout mice have been reported for Adamts6, Adamts10, Adamts17, and Adamts19 [10,11,34,42,50]. The Adamts6 knockout was identified in an ethylnitrosourea (ENU) mutagenesis screen for congenital heart defects [34].…”

Section: Mouse Models Of Adamts6 10 17 and 19 Deficiencymentioning

confidence: 99%

“…An Adamts17 knockout mouse was generated by Cre/Lox-mediated deletion of a portion of exon 4, which generates a frameshift mutation and results in ADAMTS17 mRNA depletion [50]. Similar to Adamts10 knockout mice, Adamts17 knockout mice showed some neonatal or perinatal lethality.…”

Section: Mouse Models Of Adamts6 10 17 and 19 Deficiencymentioning

confidence: 99%

The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases

et al. 2020

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Secreted a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS) proteases play crucial roles in tissue development and homeostasis. The biological and pathological functions of ADAMTS proteases are determined broadly by their respective substrates and their interactions with proteins in the pericellular and extracellular matrix. For some ADAMTS proteases, substrates have been identified and substrate cleavage has been implicated in tissue development and in disease. For other ADAMTS proteases, substrates were discovered in vitro, but the role of these proteases and the consequences of substrate cleavage in vivo remains to be established. Mutations in ADAMTS10 and ADAMTS17 cause Weill–Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities). WMS can also be caused by mutations in fibrillin-1 (FBN1), which suggests that ADAMTS10 and ADAMTS17 cooperate with fibrillin-1 in a common biological pathway during tissue development and homeostasis. Here, we compare and contrast the biochemical properties of ADAMTS10 and ADAMTS17 and we summarize recent findings indicating potential biological functions in connection with fibrillin microfibrils. We also compare ADAMTS10 and ADAMTS17 with their respective sister proteases, ADAMTS6 and ADAMTS19; both were recently linked to human disorders distinct from WMS. Finally, we propose a model for the interactions and roles of these four ADAMTS proteases in the extracellular matrix.

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“…Human mutations in ADAMTS10 and 17 are associated with related syndromes involved in alterations in skeletal development (Dagoneau et al, 2004;Morales et al, 2009). Recently, knockout mice for both Adamts10 and 17 were shown to develop the recapitulate syndromic phenotype in human (Figure 9C; Mularczyk et al, 2018;Oichi et al, 2019). Reduced hypertrophic zone and increased deposition of fibrillin-2 alter the growth plates during endochondral ossification resulting in adults with short statures.…”

Section: State-of-the-art Of Cleft Palate Repair and Palatal Reconstrmentioning

confidence: 99%

“…are glycoproteins involved in microfibril formation and elastin deposition. Also, treatment with BMP-2 can rescue terminal chondrocyte differentiation, suggesting that ADAMTS17 is important for ossification through the modulation of BMP signaling (Oichi et al, 2019).…”

Section: State-of-the-art Of Cleft Palate Repair and Palatal Reconstrmentioning

confidence: 99%

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

Paiva

Maas

Santos

et al. 2019

Front. Cell Dev. Biol.

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Craniofacial development comprises a complex process in humans in which failures or disturbances frequently lead to congenital anomalies. Cleft lip with/without palate (CL/P) is a common congenital anomaly that occurs due to variations in craniofacial development genes, and may occur as part of a syndrome, or more commonly in isolated forms (non-syndromic). The etiology of CL/P is multifactorial with genes, environmental factors, and their potential interactions contributing to the condition. Rehabilitation of CL/P patients requires a multidisciplinary team to perform the multiple surgical, dental, and psychological interventions required throughout the patient's life. Despite progress, lip/palatal reconstruction is still a major treatment challenge. Genetic mutations and polymorphisms in several genes, including extracellular matrix (ECM) genes, soluble factors, and enzymes responsible for ECM remodeling (e.g., metalloproteinases), have been suggested to play a role in the etiology of CL/P; hence, these may be considered likely targets for the development of new preventive and/or therapeutic strategies. In this context, investigations are being conducted on new therapeutic approaches based on tissue bioengineering, associating stem cells with biomaterials, signaling molecules, and innovative technologies. In this review, we discuss the role of genes involved in ECM composition and remodeling during secondary palate formation and pathogenesis and genetic etiology of CL/P. We also discuss potential therapeutic approaches using bioactive molecules and principles of tissue bioengineering for state-of-the-art CL/P repair and palatal reconstruction.

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Adamts17 is involved in skeletogenesis through modulation of BMP-Smad1/5/8 pathway

Cited by 30 publications

References 38 publications

Gentiopicroside promotes osteogenesis and prevents bone loss in ovariectomized mice by modulation of β-catenin-BMP2 signaling pathway

Gentiopicroside promotes osteogenesis and prevents bone loss in ovariectomized mice by modulation of β-catenin-BMP2 signaling pathway

The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

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