BMP-4 蛋白, 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.

骨形态发生蛋白4（BMP-4）是一种多效性配体蛋白，属于TGFβ家族。BMP-4 参与脉管系统循环，可激活血管细胞上的受体^[1]。
BMP-4/TGFβ 信号传导可被抑制性 SMAD 终止，包括 SMAD6 和 SMAD7，这些 SMAD 被激活BMP-4 广泛存在于不同动物体内，而人类的序列与大鼠高度相似（96.81 %) 和小鼠 (97.54%)。
BMP-4 由内皮细胞 (EC) 在缺氧反应中表达，并促进血管 SMC 增殖。因此，它抑制从近端肺动脉分离的平滑肌细胞 (SMC) 增殖，同时诱导从远端肺动脉分离的 SMC 增殖^[5]。
BMP-4 似乎是一种血管钙化的标志物和驱动因素，特别是在动脉粥样硬化中^[6]。
BMP-4 诱导血管生成、内皮细胞 (EC) 增殖和迁移^[7] .
BMP-4 在钙化动脉粥样硬化斑块中差异表达^[8]，作为动脉粥样硬化血管钙化与正常骨形成机制之间的链接器^[9] .
BMP-4 通过其促炎和促动脉粥样硬化作用增加斑块形成，促进氧化应激、内皮功能障碍和成骨分化^[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]

SPKHHSQRARKKNKNCRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTLVNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGCR

13-16 kDa

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

无菌粉末

Lyophilized after extensive dialysis against solution in 50 mM Na₂CO₃, 5 mM DTT, pH 11.0 or 50 mM Tris-HCL, 200 mM NaCL, 500 mM arginine, pH 8.0.

<1.0 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. 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]