Sheep Sclerostin ELISA, SOST
- Known as:
- Sheep Sclerostin Enzyme-linked immunosorbent assay test, SOST
- Catalog number:
- E14S0207
- Product Quantity:
- 96 Tests/kit
- Category:
- -
- Supplier:
- BGene
- Gene target:
- Sheep Sclerostin ELISA SOST
Related genes to: Sheep Sclerostin ELISA, SOST
- Gene:
- LRP4 NIH gene
- Name:
- LDL receptor related protein 4
- Previous symbol:
- -
- Synonyms:
- MEGF7, CLSS, LRP-4, SOST2
- Chromosome:
- 11p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-25
- Date modifiied:
- 2015-11-13
- Gene:
- SOST NIH gene
- Name:
- sclerostin
- Previous symbol:
- -
- Synonyms:
- VBCH, DAND6
- Chromosome:
- 17q21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-20
- Date modifiied:
- 2016-04-27
Related products to: Sheep Sclerostin ELISA, SOST
Related articles to: Sheep Sclerostin ELISA, SOST
- Sclerostin negatively regulates bone formation. The marketed antibody against sclerostin loop2 promoted bone formation but may have caused severe cardiovascular events in clinical use. In our published studies, sclerostin loop3 was found to be involved in inhibitory effects of sclerostin on bone formation, whereas cardiovascular protective effects of sclerostin in mice were independent of loop3. It is necessary to investigate how sclerostin loop3 participates in the inhibitory effects of sclerostin on bone formation to facilitate developing precise strategies that promote bone formation without increasing cardiovascular risk. In this study, sclerostin loop3 was identified to bind to LRP4, thereby facilitating binding of sclerostin to LRP6 in osteoblasts. Blockade of sclerostin loop3-LRP4 interaction by both Lrp4 mutation (Lrp4m) and blocking peptide (LRP4-Pep) diminished the antagonistic effect of sclerostin on Wnt/β-catenin signaling in osteoblasts in vitro. Consistently, Lrp4m promoted bone formation in Lrp4m mice in vivo. Mechanistically, osteoblast-conditional correction of Lrp4m to wild-type Lrp4 resulted in significantly lower bone formation than Lrp4m mice, indicating that the promotive effects of Lrp4m on bone formation acted in osteoblasts in vivo. Moreover, re-expression of sclerostin dramatically inhibited bone formation in sost mice, whilst the inhibitory effects of sclerostin were significantly weaker in sost.Lrp4m mice. Pharmacologically, LRP4-Pep diminished the inhibitory effects of sclerostin on bone formation in SOST mice. Taken together, osteoblastic sclerostin loop3-LRP4 interaction, as an anchor, was required by sclerostin to bind to LRP6, thereby inhibiting bone formation. Translationally, blockade of sclerostin loop3-LRP4 interaction in osteoblasts would provide precise therapeutic strategies to promote bone formation without increasing cardiovascular risk. - Source: PubMed
Publication date: 2026/04/24
Wang LuyaoTao XiaohuiJiang HewenDing ShijianZhang NingYang XinWang ShenghangZhang YihaoLi NanxiLi HaitianLi ZhanghaoWen XiaoxinSun MeihengZhong ChuanxinSo HeiwaLiu JinYu YuanyuanYue HuaLuo XianghangFerdinandy PéterZhang TaoZhang ShuZhang ZhenlinLu AipingZhang BaotingZhang Ge - Sclerostin, which has three loops, inhibits bone formation and impairs whole-body lipid and glucose metabolism. The marketed therapeutic sclerostin antibody for postmenopausal osteoporosis (POP) mainly targeting loop2 promotes bone formation and improves whole-body lipid and glucose metabolism. However, FDA/EMA warns of its cardiovascular risk. We previously demonstrate that sclerostin loop3 contributes to the inhibitory effect of sclerostin on bone formation but not its cardioprotective effect. Here we find elevated serum sclerostin levels in both POP-T2DM patients and newly-diagnosed T2DM patients and further demonstrate that sclerostin loop3 participates in the impairment effect of sclerostin on whole-body lipid and glucose metabolism in vivo. Mechanistically, specific blockade of adipocytic sclerostin loop3-LRP4 interaction attenuates the impairment effect of sclerostin on lipid and glucose metabolism in vitro and in vivo. This study provides an innovative strategy, blocking adipocytic sclerostin loop3-LRP4 interaction, to normalize lipid and glucose metabolism in POP-T2DM patients, in cardiovascular safety. - Source: PubMed
Publication date: 2026/01/16
Jiang HewenTao XiaohuiYu SifanZhang YihaoMa YuanLi NanxiWang ShenghangZhang NingYang XinDing ShijianZhong ChuanxinLi HaitianLi ZhanghaoWen XiaoxinZhang HuaruiChen ZefengSun MeihengLuo HangRen MeishenLei ChongguangYu YuanyuanLiu JinZhang ZongkangLyu AipingSheng HuiLi DijieWang LuyaoZhang GeZhang Bao-Ting - The interaction of sclerostin (Scl) with the low-density lipoprotein receptor-related protein 4 (LRP4) leads to a marked reduction in bone formation by inhibiting the Wnt/β-catenin pathway. To characterize the Scl-LRP4 binding interface, we sorted a combinatorial library of Scl variants and isolated variants with reduced affinity to LRP4. We identified Scl single-mutation variants enriched during the sorting process and verified their reduction in affinity toward LRP4-a reduction that was not a result of changes in the variants' secondary structure or stability. We found that Scl positions K75 (loop 1) and V136 (loop 3) are critical hotspots for binding to LRP4. Our findings establish the foundation for targeting these hotspots for developing novel therapeutic strategies to promote bone formation. - Source: PubMed
Publication date: 2024/10/23
Katchkovsky SvetlanaMeiri ReutLacham-Hartman ShiranOrenstein YaronLevaot NoamPapo Niv - LRP4 is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of LRP4 that specifically affect the canonical WNT signaling pathway are known to be associated with Cenani-Lenz syndactyly syndrome or the overlapping condition sclerosteosis. However, site-specific pathogenic variants of LRP4 have been associated with the congenital myasthenic syndrome (CMS) type 17 with no abnormal bone phenotype. Only two studies reported biallelic variants of LRP4 associated with CMS17 that presented during childhood. All three reported variants (NM_002334.4: p.Glu1233Ala, p.Glu1233Lys, or p.Arg1277His) are located within the 3'-edge of the third β-propeller domain of LRP4. We report on a patient with a biallelic variant of the LRP4 gene presenting with a severe and neonatal lethal phenotype; we also provide a literature review of the previously reported patients. A female neonate, born to healthy consanguineous parents, presented with severe hypotonia, congenital diaphragmatic hernia, pulmonary hypertension, and progressive hypoxemia. Two of her siblings presented with a similar condition in the past, and all three died shortly after birth. Clinical exome sequencing revealed homozygosity for the pathogenic variant NM_002334.4:c.3698A > C (p.[Glu1233Ala]). - Source: PubMed
Publication date: 2023/12/13
Al Jabry TariqAl-Hashmi NadiaAbdelhadi BasemAl-Maawali Almundher - Pathogenic variants disrupting the binding between sclerostin (encoded by SOST) and its receptor LRP4 have previously been described to cause sclerosteosis, a rare high bone mass disorder. The sclerostin-LRP4 complex inhibits canonical WNT signaling, a key pathway regulating osteoblastic bone formation and a promising therapeutic target for common bone disorders, such as osteoporosis. In the current study, we crossed mice deficient for Sost (Sost) with our p.Arg1170Gln Lrp4 knock-in (Lrp4) mouse model to create double mutant Sost;Lrp4 mice. We compared the phenotype of Sost mice with that of Sost;Lrp4 mice, to investigate a possible synergistic effect of the disease-causing p.Arg1170Trp variant in Lrp4 on Sost deficiency. Interestingly, presence of Lrp4 alleles partially mitigated the Sost phenotype. Cellular and dynamic histomorphometry did not reveal mechanistic insights into the observed phenotypic differences. We therefore determined the molecular effect of the Lrp4 allele by performing bulk RNA sequencing on Lrp4 primary osteoblasts. Unexpectedly, mostly genes related to bone resorption or remodeling (Acp5, Rankl, Mmp9) were upregulated in Lrp4 primary osteoblasts. Verification of these markers in Lrp4, Sost and Sost;Lrp4 mice revealed that sclerostin deficiency counteracts this Lrp4 effect in Sost;Lrp4 mice. We therefore hypothesize that models with two inactivating Lrp4 alleles rather activate bone remodeling, with a net gain in bone mass, whereas sclerostin deficiency has more robust anabolic effects on bone formation. Moreover, these effects of sclerostin and Lrp4 are stronger in female mice, contributing to a more severe phenotype than in males and more detectable phenotypic differences among different genotypes. - Source: PubMed
Publication date: 2023/12/05
Hendrickx GretlBoudin EvelineMateiu LigiaYorgan Timur ASteenackers EllenKneissel MichaelaKramer InaMortier GeertSchinke ThorstenVan Hul Wim