Recombinant Human Noggin

Recombinant human Noggin Growth Beta Factor (Noggin) is a secreted glycoprotein that functions as a potent antagonist of the Bone Morphogenetic Protein (BMP) signaling pathway, a key regulator of embryogenesis and tissue morphogenesis. Discovered as a dorsalizing factor in Xenopus embryos, Noggin binds BMP ligands such as BMP2, BMP4, and BMP7 with high affinity, thereby preventing their receptor-mediated activation (Zimmerman et al., 1996; Groppe et al., 2002). This regulatory role positions Noggin as a crucial modulator of developmental processes, tissue homeostasis, and pathological conditions associated with dysregulated BMP signaling. This paper provides an integrative overview of recombinant human Noggin’s molecular features, mechanisms of BMP inhibition, and physiological functions. Furthermore, it explores emerging therapeutic and translational implications of Noggin activity in bone regeneration, neuroprotection, and cancer biology. Synonyms commonly used for Noggin—such as SYM1, SYNS1, and NOG—are also reviewed to elucidate their relevance in genomic and proteomic databases.

Introduction Noggin is a highly conserved secreted protein encoded by the NOG gene, first characterized for its ability to induce dorsalization in developing embryos (Smith & Harland, 1992). It plays a central role in regulating BMP-mediated pathways that govern skeletal development, neural differentiation, and organogenesis (Brunet et al., 1998). In humans, recombinant Noggin has been leveraged as a research reagent to study BMP inhibition and as a potential therapeutic candidate in degenerative or fibrotic diseases. Synonyms such as SYM1, SYNS1, and NOG appear across genomic databases, reflecting its widespread recognition in developmental biology and regenerative research contexts.

Molecular Characteristics of Noggin Noggin is a 232–amino acid glycoprotein that forms disulfide-linked homodimers. Structural analyses reveal a cystine-knot motif typical of growth factor antagonists, facilitating its interaction with the BMP dimer interface (Groppe et al., 2002). Post-translational glycosylation enhances its stability and secretion efficiency. By forming nonproductive BMP–Noggin complexes, Noggin prevents ligand–receptor engagement, effectively silencing downstream SMAD phosphorylation and transcriptional activation (Zimmerman et al., 1996).

Inhibition of BMP Signaling by Noggin Noggin inhibits BMP signaling by high-affinity binding to BMP2, BMP4, and BMP7 ligands (Piccolo et al., 1996). This interaction masks receptor-binding epitopes, thereby blocking activation of BMP type I and II receptors. Noggin’s inhibitory effect modulates the balance between BMP and other transforming growth factor-beta (TGF-β) family pathways, influencing processes such as osteoblast differentiation, neuronal patterning, and chondrogenesis (Gazzerro & Canalis, 2006).

Physiological Functions of Noggin Noggin’s biological functions are critical across multiple systems. During embryonic development, it regulates neural tube closure, somite differentiation, and limb morphogenesis. In adults, Noggin maintains skeletal homeostasis by restraining BMP-induced ossification and promoting synovial joint integrity (Brunet et al., 1998; Devlin et al., 2003). Dysregulation of NOG expression is implicated in skeletal dysplasias, fibrosis, and neurodegenerative diseases.

Therapeutic Implications of Noggin Due to its selective antagonism of BMP signaling, recombinant Noggin holds strong therapeutic promise. Preclinical studies demonstrate its ability to inhibit ectopic bone formation, protect dopaminergic neurons, and attenuate fibrosis (Gazzerro & Canalis, 2006; Lim et al., 2016). Noggin-based therapeutics are being explored for osteoarthritis, spinal cord injury, and glioblastoma, though challenges such as protein stability and targeted delivery remain.

Clinical Studies and Translational Research Recent translational research efforts integrate Noggin into biomaterial scaffolds and tissue engineering systems to control local BMP activity and promote balanced regeneration. Studies using Noggin-modified hydrogels enhance neural stem cell survival and modulate osteogenic differentiation (Lim et al., 2016; Katagiri & Watabe, 2016). Although clinical applications are still in early evaluation, the recombinant Noggin platform represents a promising approach for regenerative and anti-fibrotic therapies.

The ED50 was determined by measuring the inhibition of alkaline phosphatase production induced by 5.0 ng/mL BMP-4 in murine ATDC-5 cells. The expected ED50 for this inhibition is less than 3 ng/mL of Noggin, corresponding to a specific activity of 3.3 × 10^5 units/mg.

Q13253.1

MQHYLHIRPA PSDNLPLVDL IEHPDPIFDP KEKDLNETLL RSLLGGHYDP GFMATSPPED RPGGGGGAAG GAEDLAELDQ LLRQRPSGAM PSEIKGLEFS EGLAQGKKQR LSKKLRRKLQ MWLWSQTFCP VLYAWNDLGS RFWPRYVKVG SCFSKRSCSV PEGMVCKPSK SVHLTVLRWR CQRRGGQRCG WIPIQYPIIS ECKCSC

Lyophilized

Produced in Escherichia coli, this recombinant human Noggin is a non-glycosylated, non-disulfide-linked homodimer composed of two polypeptide chains, each 206 amino acids in length. The total molecular weight of the homodimer is approximately 46.3 kDa. Noggin is purified through proprietary chromatographic methods to ensure high purity and quality.

This Protein was lyophilized from a 0.2μm filtered solution in 30% CH3CN, 0.1% TFA.

This lyophilized protein is stable for six to twelve months when stored desiccated at -20°C to -70°C. After aseptic reconstitution, this protein may be stored at 2°C to 8°C for one month or at -20°C to -70°C in a manual defrost freezer. Avoid Repeated Freeze Thaw Cycles. See Product Insert for exact lot specific storage instructions. To enhance long-term storage stability, it is recommended to add a carrier protein (such as 0.1% HSA or BSA).

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1. Harland RM. et al. (1998) Science 280: 1455