BMP-4 Protein, Human

Bone morphogenetic protein 4 (BMP-4) is a polymorphic ligand protein belonging to the TGF-β family, which is involved in the circulation of the vascular system and can activate receptors on vascular cells^[1]. BMP-4 binds to type I receptors (ALK-2/-3/-6) and type II receptors (BMPR2, ACVR2A)^[2] to increase plaque formation and promote oxidative stress, endothelial dysfunction, and osteogenic differentiation through its pro-inflammatory and pro-atherogenic effects^[3]. BMP-4 Protein, Human has a total length of 116 amino acids (S293-R408), is expressed in E. coli cells with tag free.

Bone Morphogenetic Protein 4 (BMP-4) is a ligand protein with pleiotropic, belongs to TGFβ family. BMP-4 involves in the vasculature circulation and can activate receptors on vascular cells^[1].
BMP-4/TGFβ signaling can be terminated by inhibitory SMADs including SMAD6 and SMAD7, which are activated and induced by BMP signaling and switch off BMP signaling via multiple mechanisms^[4].
BMP-4 is widely found in different animals, while the sequence in human is highly similar to Rat (96.81%), and mouse (97.54%).
BMP-4 is expressed by endothelial cells (ECs) in response to hypoxia and promotes vascular SMC proliferation. Therefore it inhibits the proliferation of smooth muscle cells (SMCs) isolated from the proximal pulmonary artery while induces proliferation of SMCs isolated from distal pulmonary arteries^[5].
BMP-4 appears to be a marker and driver of vascular calcification, particularly in atherosclerosis^[6].
BMP-4 induces angiogenesis, endothelial cells (ECs) proliferation, and migration^[7].
BMP-4 is differentially expressed in calcified atherosclerotic plaques^[8], serves as the linkers between atherosclerotic vascular calcification with mechanisms of normal bone formation^[9].
BMP-4 increases plaque formation via their pro-inflammatory and pro-atherogenic effects, promoting oxidative stress, endothelial dysfunction and osteogenic differentiation^[3].

BMP-4 (1 ng/mL for 4-5 d; 10 ng/mL for 3-4 d; 100 ng/mL for 2 d) induces a synchronous wave of differentiation occurred, characterized by flattened, enlarged cells with reduced proliferation^[10].
BMP-4 (100 ng/mL; 7 d) initiates human embryonic stem cell differentiation to trophoblast^[10].
BMP4 (10 or 100 ng/mL; 24 h) significantly increases the number of mesenchymal condensations by approximately 50%^[11].

Measured by its ability to induce alkaline phosphatase production by ATDC5 mouse chondrogenic cells.The ED₅₀ for this effect is < 60 ng/mL.

• 
  Measured by its ability to induce alkaline phosphatase production by ATDC5 mouse chondrogenic cells. The ED₅₀ for this effect is 0.9255 ng/mL, corresponding to a specific activity is 1.08×106 U/mg.

Human

E. coli

Tag Free

P12644 (S293-R408)

652  [NCBI]

Full Length of Mature Protein

SPKHHSQRARKKNKNCRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTLVNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGCR

Approximately 13 kDa, based on SDS-PAGE under reducing conditions.

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

Lyophilized powder.

1.Lyophilized from a 0.22 μm filtered solution of 50 mM Na₂CO₃, 5 mM DTT, pH 11.0.
2.Lyophilized from a 0.22 μm filtered solution of 50 mM Tris-HCl, 200 mM NaCL, 500 mM arginine, pH 8.0.
3.Lyophilized from a 0.22 μm filtered solution of 0.1% TFA, 30% Acetonitrile, pH 2.5.
Please refer to the lot-specific COA for specific buffer information.
Note: For SPR assay, please replace the buffer. Primary amine components (e.g., Tris, imidazole) can affect protein-coupled chips.

<1 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]. Yang P, et al. The role of bone morphogenetic protein signaling in vascular calcification. Bone. 2020 Dec;141:115542.  [Content Brief]

  [2]. Gieseler GM, et al. Solubilization and renaturation of biologically active human bone morphogenetic protein-4 from inclusion bodies. Biotechnol Rep (Amst). 2018 Apr 4;18:e00249.  [Content Brief]

  [3]. Miyazawa K, et al. Regulation of TGF-β Family Signaling by Inhibitory Smads. Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3):a022095.  [Content Brief]

  [4]. Herrera B, et al. A rapid and sensitive bioassay for the simultaneous measurement of multiple bone morphogenetic proteins. Identification and quantification of BMP4, BMP6 and BMP9 in bovine and human serum. BMC Cell Biol. 2009 Mar 19;10:20.  [Content Brief]

  [5]. Yang X, et al. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res. 2005 May 27;96(10):1053-63.  [Content Brief]

  [6]. Scimeca M, et al. Plaque calcification is driven by different mechanisms of mineralization associated with specific cardiovascular risk factors. Nutr Metab Cardiovasc Dis. 2019 Dec;29(12):1330-1336.  [Content Brief]

  [7]. David L, et al. Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev. 2009 Jun;20(3):203-12.  [Content Brief]

  [8]. Dhore CR, et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1998-2003.  [Content Brief]

  [9]. Demer LL, et al. Mechanism of calcification in atherosclerosis. Trends Cardiovasc Med. 1994 Jan-Feb;4(1):45-9.  [Content Brief]

  [10]. Boström K, et al. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993 Apr;91(4):1800-9.  [Content Brief]

  [11]. Xu RH, et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol. 2002 Dec;20(12):1261-4.  [Content Brief]

  [12]. Hatakeyama Y, et al. Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis. J Cell Biochem. 2004 Apr 15;91(6):1204-17.  [Content Brief]