GMP Noggin 蛋白, Human (HEK293, His)

Noggin protein is an important BMP inhibitor that plays an indispensable role in the neural tube, somite growth, cartilage morphogenesis, and joint formation. Its homodimeric structure promotes significant interactions with GDF5 and possibly GDF6, inhibiting chondrocyte differentiation. GMP Noggin Protein, Human (HEK293, His) is the recombinant human-derived Noggin protein, expressed by HEK293 , with C-6*His labeled tag.

1. Noggin 的特点
Noggin 属于 TGF-β 超家族拮抗剂，并与 Chordin、Gremlin 等同属 BMP 结合蛋白家族，通过分泌型蛋白机制发挥作用，对于骨骼的正常发育至关重要^[1][5][6]。Noggin 是由二硫键连接的糖基化同源二聚体，含保守的半胱氨酸结结构域 (cysteine-knot domain)。Noggin 可特异性靶向 BMP-2、-4、-7 等配体而抑制其与受体结合^[3]，对 hBMP-4 具有高亲和力，对 hBMP-4 具有较低亲和力，还是 hBMP-7 的拮抗剂^[5]。Noggin 结合 BMPs (如 BMP-2/-4) 阻断其与 I 型 (BMPR-IA/IB) 和 II 型 (BMPR-II) 丝氨酸/苏氨酸激酶受体的相互作用，抑制 Smad1/5/8 磷酸化及下游转录。
Noggin 参与骨分化调控：在人间充质干细胞 (HMSC) 中，Noggin 协同 T 细胞炎症因子 (TTII) 或 Dexamethasone (HY-14648) 诱导碱性磷酸酶活性与矿化，上调 BMP-2 和骨钙素 (Osteocalcin) 表达，但不影响 Runx2^[1]。
Noggin 参与干细胞多能性维持：在人胚胎干细胞 (hESC) 中抑制 BMP4 诱导的分化，维持 Oct4、Nanog 等多能性基因表达，促进细胞增殖^[2]。
Noggin 抑制血管生成：在人脐静脉内皮细胞 (HUVEC) 中阻断 BMP-4 信号，抑制细胞迁移、管形成及血管生成，下调 BMP-4 mRNA 水平^[3]。
Noggin 促进神经髓鞘化：在少突胶质细胞分化中，解除 BMP 对 Sox10/Nkx2.2 的抑制，促进 Myelin Basic Protein (MBP) 表达及髓鞘形成^[4]。

2. Noggin 的应用
Noggin 与 BMP 联用调控成骨-破骨平衡，用于骨缺损修复，而适用于骨组织工程^[1]。Noggin 还维持 hESC 多能性，可优化少突胶质前体细胞分化，用于多发性硬化等髓鞘疾病模型的研究^[2]。Noggin 还通过抑制内皮细胞迁移防治肿瘤血管生成，具有抗癌活性。Noggin 预处理少突胶质前体细胞可增强其在 BMP 缺陷 shiverer 小鼠的髓鞘化^[4]。

Noggin Protein (人源；200 ng/mL；10 d 或 3 周) 在人间充质干细胞 (HMSC) 中诱导碱性磷酸酶活性与矿化，与 T 细胞炎症因子 (TTII：TNF-α，TGF-β，IFN-γ，IL-17) 或 100 nM Dexamethasone (HY-14648) 协同作用，可上调 BMP-2 和骨钙素基因表达，但不影响 Runx2 表达^[1]。
Noggin Protein (人源；400 ng/mL；14 d) 在人胚胎干细胞 (hESC) 中维持多能性，抑制自发分化，促进细胞增殖，与 Matrigel 联用可增强 Oct4 和 SSEA-4 表达^[2]。

Noggin Protein (人源；0.45-0.9 mg/kg；皮下渗透泵植入；4 周) 在 C57BL/6 和 apoE^-/- 小鼠中可拮抗 BMP4 诱发的高血压、血管 NADPH 氧化酶活化以及内皮功能障碍^[7]。

Measured by its ability to inhibit BMP-2-induced alkaline phosphatase production by ATDC5 mouse chondrogenic cells The ED₅₀ for this effect is ≤0.13 μg/mL in the presence of 2000 ng/mL of Recombinant Human BMP‑2.

Human

HEK293

C-6*His

Q13253 (Q28-C232)

9241  [NCBI]

Full Length of Mature Protein

QHYLHIRPAPSDNLPLVDLIEHPDPIFDPKEKDLNETLLRSLLGGHYDPGFMATSPPEDRPGGGGGAAGGAEDLAELDQLLRQRPSGAMPSEIKGLEFSEGLAQGKKQRLSKKLRRKLQMWLWSQTFCPVLYAWNDLGSRFWPRYVKVGSCFSKRSCSVPEGMVCKPSKSVHLTVLRWRCQRRGGQRCGWIPIQYPIISECKCSC

Approximately 28-32 kDa

Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末.

Lyophilized a 0.22 μm filtered solution of 20mM PB, 500mM NaCl, 2mM EDTA, pH 7.4.

<0.01 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in injection water.

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Rifas L. The role of noggin in human mesenchymal stem cell differentiation. J Cell Biochem. 2007 Mar 1;100(4):824-34.  [Content Brief]

  [2]. Chaturvedi G, et al. Noggin maintains pluripotency of human embryonic stem cells grown on Matrigel. Cell Prolif. 2009 Aug;42(4):425-33.  [Content Brief]

  [3]. Kang HW, et al. In vitro and In vivo imaging of antivasculogenesis induced by Noggin protein expression in human venous endothelial cells. FASEB J. 2009 Dec;23(12):4126-34.  [Content Brief]

  [4]. Izrael M, et al. Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci. 2007 Mar;34(3):310-23.  [Content Brief]

  [5]. Groppe J, et al. Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 2002 Dec 12;420(6916):636-42.  [Content Brief]

  [6]. Brunet LJ, et al. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 1998 May 29;280(5368):1455-7.  [Content Brief]

  [7]. Miriyala S, et al. Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation. Circulation. 2006 Jun 20;113(24):2818-25.Miriyala S, et al. Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation. Circulation. 2006 Jun 20;113(24):2818-25.  [Content Brief]