• Title/Summary/Keyword: Sost

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Conformational Dynamics of Sclerostin-LRP6 Complex Analyzed by HDX-MS

  • Jeong, Yejing;Kim, Jinuk;Choi, Hee-Jung;Chung, Ka Young
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.527-535
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    • 2021
  • Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDX-MS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.

Reflection Characteristics of Eco Block on Seabed

  • Kim, Jeong-Seok;Lee, Joong-Woo;Kang, Seok-Jin;Lee, Yong-Hun
    • Journal of Navigation and Port Research
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    • v.38 no.4
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    • pp.421-427
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    • 2014
  • In order to protect coastal facilities mainly from wave and current actions, the self-locking eco blocks constituting elements of protecting shore structures against scouring were designed. These blocks are adapted to the sloping bottom, coastal dunes, and submerged coastal pipelines, counteracting the destructive and erosive impulse action. A series of laboratory experiments has been conducted to investigate the reflection of water waves over and against a train of protruded or submerged shore structures and compare the reflecting capabilities of incident waves including wave forces. In this study the hydraulic model experiment was conducted to identify the performance of newly designed water affinity eco blocks to keep the coast slope and bottom mound from scouring by reduction of the wave reflection and to convince stability of the block placement. Revised design of each block element was also tested for field conditions. From the result of experiments, the field applicability of the developed blocks and placement was discussed afterward.

Marina Development Impact on the Tranquility of Small Coast Harbor

  • Lee, Dong-Hyun;Lee, Joong-Woo;An, Hyo-Jae;Kim, Kang-Min
    • Journal of Navigation and Port Research
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    • v.38 no.6
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    • pp.673-681
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    • 2014
  • Due to the increased demand for safety and security requirements on the port infrastructure, the harbor tranquility is one of the important parameter in the mooring basin of harbor. It relates keenly to berthing/unberthing and cargo handling works but also it is an important indicator to get the minimum water area as the safe refuge. Hupo harbor is a national coastal harbor located in east coast of Korea and a development plan for a new marina near the entrance is being carried out including berth layouts, breakwater extensions, 300m marina berths, dredging and land reclamation works. The new plan will impact on calmness of the existing port. Therefore, it is necessary to analyze in complex the variation of wave height and direction caused by wave refraction, diffraction, shoaling and reflection from the incident waves from outside the harbor. In order to check the calmness inside a harbor, the numerical models are being used currently need fundamental reviews according to the difference of results which depend on their respective features. In this study, hence, it was introduced the validity of numerical models by comparing the computational results with the hydraulic model experiment. The current investigations contribute to the existing development recommendations and provide further solutions for port planning.

Role of Wnt signaling in fracture healing

  • Xu, Huiyun;Duan, Jing;Ning, Dandan;Li, Jingbao;Liu, Ruofei;Yang, Ruixin;Jiang, Jean X.;Shang, Peng
    • BMB Reports
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    • v.47 no.12
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    • pp.666-672
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    • 2014
  • The Wnt signaling pathway is well known to play major roles in skeletal development and homeostasis. In certain aspects, fracture repair mimics the process of bone embryonic development. Thus, the importance of Wnt signaling in fracture healing has become more apparent in recent years. Here, we summarize recent research progress in the area, which may be conducive to the development of Wnt-based therapeutic strategies for bone repair.

Gingival crevicular fluid levels of sclerostin in chronic periodontitis and healthy subjects

  • Esfahrood, Zeinab Rezaei;Yadegari, Zahra;Veysari, Setareh Kazemi;Kadkhodazadeh, Mahdi
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.44 no.6
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    • pp.289-292
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    • 2018
  • Objectives: Chronic periodontitis is a common inflammatory disease of the oral cavity that causes destruction of periodontal tissues and bone around the teeth. Sclerostin is a protein encoded by the SOST gene. In this study, gingival crevicular fluid (GCF) levels of sclerostin in patients with chronic periodontitis were compared with those of healthy subjects. Materials and Methods: In this case-control study, a total of 40 subjects were enrolled and divided into the healthy group (n=23) and chronic periodontitis group (n=17). GCF samples were collected, and the concentration of sclerostin was evaluated using enzyme-linked immunosorbent assay. Comparison of significance between groups was assessed using Mann-Whitney U test. Results: Sclerostin concentration was significantly higher in the chronic periodontitis group compared with the healthy group (P<0.005). Conclusion: Despite the limitations of this study, sclerostin can be a possible marker for assessment of periodontal health status.

Numerical Analysis of Reflection Characteristics of Perforated Breakwater with a Resonant Channel (공진수로 내장형 유공방파제의 반사특성에 관한 수치해석 연구)

  • Kim, Jeong-Seok;Seo, Ji-Hye;Lee, Joong-Woo;Park, Woo-Sun
    • Journal of Navigation and Port Research
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    • v.38 no.5
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    • pp.503-509
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    • 2014
  • In this study, a new concept perforated breakwater is proposed, which is having resonant channels. In the channel, perforated plate is installed for dissipating wave energy induced by flow separations. The breakwater has two advantages compared with conventional perforated breakwater having wave chamber with slotted walls. One is easy to control the target wave condition for dissipating wave energy, and the other is having the high structural safety because the structural members are not exposed to impact waves, directly. To evaluate wave reflection characteristics of the proposed breakwater, numerical experiment was carried out by using Galerkin's finite element model based on the linear potential theory. The results indicated that considerable energy dissipation occurs near the resonant period of channel, and wave reflection characteristics are affected by channel shape, location and opening ratio.

Design Conditions for Dolphin Berth by Tanker Fleet Analysis

  • Kang, Seok-Jin;Lee, Joong-Woo;Lee, Dong-Hyun;Kim, Hee-Jae
    • Journal of Navigation and Port Research
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    • v.37 no.6
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    • pp.647-653
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    • 2013
  • Energy acquisition due to the increase of oil price is one of the most important issues and policy for most countries. Various tankers have been built in the world and sent to the trade market. It is necessary to build the port infrastructure and facilities to give them proper services such as mooring, packing, storing, and transshipment, etc. However, the domestic guidelines or standards for design and construction for the dolphin berth among these facilities are out of date and do not meet the recent trend of tanker types. Therefore, it requires amendment on the guidelines or standards. In this study, a detailed analysis of the tanker fleet, covering 8,000 ships under operation and order to build, is made to estimate the proper PBL(Parallel Body Length) of each tanker class. After discussion and comparison on the dolphin berth design and construction codes of various countries, those are the leading countries of tanker operation and management, suggestion was made to amend on the design code. The referred codes are of Korea, Japan, UK, USA, and Canada. The analysis of tanker fleet shows the PBL as 0.45L under the normal ballast condition. In order to verify the deduced amendment on the domestic design code for dolphin berth, it was selected one of the domestic dolphin berth, located at the Yeosu oil terminal, which is almost completed to construct. The design criteria and expected tankers to moor in that terminal were analyzed and the appropriateness and countermeasure for deficiency were summarized.

Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential

  • Fang, Ting-Ting;Sun, Xiao-Jing;Chen, Jie;Zhao, Yan;Sun, Rui-Xia;Ren, Ning;Liu, Bin-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10513-10524
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    • 2015
  • Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.