Noggin Protein, 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. 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].

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 27-36 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

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

Lyophilized powder

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]