GMP Noggin Protein, 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. Characteristics of Noggin
Noggin belongs to the TGF-β superfamily antagonist and belongs to the BMP binding protein family together with Chordin and Gremlin. It works through a secretory protein mechanism and is essential for normal bone development^[1][5][6]. Noggin is a glycosylated homodimer linked by disulfide bonds and contains a conserved cysteine-knot domain. Noggin can specifically target ligands such as BMP-2, -4, and -7 and inhibit their binding to receptors^[3]. It has a high affinity for hBMP-4 and a low affinity for hBMP-4. It is also an antagonist of hBMP-7^[5]. Noggin binds to BMPs (such as BMP-2/-4) and blocks their interaction with type I (BMPR-IA/IB) and type II (BMPR-II) serine/threonine kinase receptors, inhibiting Smad1/5/8 phosphorylation and downstream transcription.
Noggin is involved in the regulation of bone differentiation: In human mesenchymal stem cells (HMSCs), Noggin synergizes with T cell inflammatory factor (TTII) or Dexamethasone (HY-14648) to induce alkaline phosphatase activity and mineralization, upregulates BMP-2 and osteocalcin expression, but does not affect Runx2^[1].
Noggin is involved in the maintenance of stem cell pluripotency: In human embryonic stem cells (hESCs), it inhibits BMP4-induced differentiation, maintains the expression of pluripotency genes such as Oct4 and Nanog, and promotes cell proliferation^[2].
Noggin inhibits angiogenesis: It blocks BMP-4 signaling in human umbilical vein endothelial cells (HUVEC), inhibits cell migration, tube formation and angiogenesis, and downregulates BMP-4 mRNA levels^[3].
Noggin promotes nerve myelination: In oligodendrocyte differentiation, it relieves the inhibition of Sox10/Nkx2.2 by BMP, promotes Myelin Basic Protein (MBP) expression and myelination^[4].

2. Application of Noggin
Noggin is used in combination with BMP to regulate the balance of osteoblast-osteoclast, which is used for bone defect repair and is suitable for bone tissue engineering^[1]. Noggin also maintains the pluripotency of hESC, can optimize the differentiation of oligodendrocyte precursor cells, and is used in the study of myelin disease models such as multiple sclerosis^[2]. Noggin also has anti-cancer activity by inhibiting endothelial cell migration and preventing tumor angiogenesis. Pretreatment of oligodendrocyte precursor cells with Noggin can enhance their myelination in BMP-deficient shiverer mice^[4].

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 25-33 kDa,based on SDS-PAGE under reducing conditions.

≥ 95%, as determined by reducing SDS-PAGE.

Lyophilized powder.

Lyophilized from a 0.22 μm filtered solution of 20 mM PB, 500 mM NaCl, 2 mM 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]