Noggin 蛋白, Human (CHO)

Noggin is an antagonist of bone morphogenetic proteins (BMPs) and a member of the TGF-β superfamily, existing as a homodimer. Noggin binds to BMP-2/-4/-7 and inhibits their binding to BMPR-I/II receptors, thereby synergistically inducing bone differentiation in HMSCs, maintaining pluripotency in hESCs, inhibiting angiogenesis in HUVECs, and promoting myelination in oligodendrocytes, exerting neural activity^[1][2][3][4]. Noggin Protein, Human (CHO) is a recombinant human Noggin protein expressed in CHO cells with tag-free.

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]。

1.ED₅₀ < 2.5 ng/mL, measured in a bioassay using ATDC5 cells in the presence of 10 ng/mL human BMP-4.
2.Measured by its ability to inhibit BMP-4-induced alkaline phosphatase production by ATDC5 mouse chondrogenic cells. The ED₅₀ for this effect is ≤43.8 ng/mL in the presence of 50 ng/mL of Recombinant Human BMP-4 (HY-P7007).

• 
  Measured by its ability to inhbit BMP-4-induced alkalnephosphatase production by ATDC5 mouse chondrogenic cells in the presence of Recombinant Human BMP-4 (40 ng/mL), with an ED₅₀ of 4 ng/mL.

Human

CHO

Tag Free

Q13253 (Q28-C232)

9241  [NCBI]

Full Length of Mature Protein

QHYLHIRPAPSDNLPLVDLIEHPDPIFDPKEKDLNETLLRSLLGGHYDPGFMATSPPEDRPGGGGGAAGGAEDLAELDQLLRQRPSGAMPSEIKGLEFSEGLAQGKKQRLSKKLRRKLQMWLWSQTFCPVLYAWNDLGSRFWPRYVKVGSCFSKRSCSVPEGMVCKPSKSVHLTVLRWRCQRRGGQRCGWIPIQYPIISECKCSC

Approximately 25-31 kDa due to the glycosylation.

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

无菌粉末

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4. Normally 8% trehalose is added as protectant before lyophilization.

<0.2 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

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]