Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway – activation via phosphorylation .
Bone morphogenetic protein 2 (BMP2) gene expression – upregulation .
Osteopontin gene expression – regulation ).
Note: The primary role of β-Glycerol phosphate disodium salt pentahydrate is to serve as a source of inorganic phosphate (Pi) for hydroxyapatite formation and as an intracellular signaling molecule. [2]

When added to osteogenic differentiation media, the inorganic phosphate (Pi) released from β-Glycerol phosphate disodium salt pentahydrate acts as an intracellular signaling molecule. It regulates the expression of several osteogenic genes, including osteopontin (in murine cementoblasts) and BMP2. [2]
Treatment of cells incapable of true osteogenic differentiation with high concentrations (≥2 mM) of β-Glycerol phosphate disodium salt pentahydrate can lead to dystrophic (non-osteogenic) mineralization, which can be falsely detected by common stains like Alizarin Red S or Von Kossa, potentially leading to false-positive conclusions about osteogenic potential. [2]
Pi from β-Glycerol phosphate disodium salt pentahydrate increases BMP2 mRNA expression through two independent pathways: activation of the ERK signaling pathway and activation of the cyclic-AMP/protein-kinase-A (cAMP/PKA) pathway. Inhibition of ERK completely blocked the Pi-mediated increase in BMP2 expression. [2]
Pi activation of the ERK signaling pathway is biphasic, mediated by two independent phosphorylation events separated by several hours. Only the second phosphorylation event leads to ERK exerting its effect on osteogenic gene expression. [2]

To distinguish between bone-specific hydroxyapatite mineralization and non-specific dystrophic mineralization (a potential pitfall when using β-Glycerol phosphate disodium salt pentahydrate), a complex set of analytical methods is recommended beyond simple histochemical stains. These methods include quantitative wavelength-dispersive X-ray spectroscopy to determine the calcium-to-phosphate (Ca/P) ratio (bone-specific hydroxyapatite has a ratio of 1.67), transmission electron microscopy to characterize the oriented, needle-shaped crystal growth specific to hydroxyapatite versus unorganized deposits, selected area electron diffraction analysis to compare crystal diffraction patterns, and Raman spectroscopy to analyze phosphate-oxygen bond characteristics. [2]

β-Glycerol phosphate disodium salt pentahydrate was used as a critical component in formulating the thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel for intratumoral drug delivery. [4]
The final injectable formulation contained 9% (w/w) β-Glycerol phosphate disodium salt pentahydrate, 1.8% (w/w) chitosan, and DTX (1 or 4 mg/mL). The β-GP was dissolved in deionized water to make a solution, chilled, and then added dropwise to an acidic chitosan solution (containing dissolved DTX) under stirring to form the pre-gel solution. [4]
For the in vivo antitumor efficacy study, H22 tumor-bearing ICR mice were given a single intratumoral injection of the DTX-C/GP hydrogel at a DTX dose of 20 mg/kg. Tumor growth and body weight were monitored over 21 days. [4]
For the pharmacokinetic and biodistribution study, H22 tumor-bearing mice received a single intratumoral injection of the DTX-C/GP hydrogel at a DTX dose of 20 mg/kg. Blood and tissue samples (tumor, heart, liver, spleen, lung, kidney) were collected at time points up to 21 days post-injection for analysis. [4]

Absorption, Distribution and Excretion
Peak serum phosphate concentrations are reached within 4 hours. The generated inorganic phosphate is excreted in the urine. A small amount of glycerophosphate may be excreted unchanged in the urine. Metabolism/Metabolites Glycerophosphate is hydrolyzed to produce inorganic phosphate. The extent of this reaction depends on the activity of serum alkaline phosphatase. Biological Half-Life The elimination half-life of inorganic phosphate is 2.06 hours.

During the 21-day study period, no systemic toxicity or local adverse reactions (e.g., necrosis) were observed in mice treated with either blank C/GP hydrogel or DTX-loaded C/GP hydrogel (DTX-C/GP). The body weight of the DTX-C/GP group steadily increased and remained within the normal range. This indicates that the hydrogel formulation containing β-glycerophosphate disodium pentahydrate has good local tolerability. [4] This study attributed the reduction in systemic toxicity of DTX (compared to intravenous DTX solution) to the local delivery and sustained release of the C/GP hydrogel, thereby minimizing the distribution of the drug to normal tissues. [4]

[1]. Inhibition of the nucleotidase effect of alkaline phosphatase by beta-glycerophosphate. Nature. 1968 Jul 6;219(5149):73-5.

[2]. Effects of dexamethasone, ascorbic acid and β-glycerophosphate on the osteogenic differentiation of stem cells in vitro. Stem Cell Res Ther. 2013;4(5):117.

[3]. Mechanism of action of beta-glycerophosphate on bone cell mineralization. Calcif Tissue Int. 1992;51(4):305-311.

[4]. Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/β-glycerophosphate hydrogel loaded with docetaxel. AAPS PharmSciTech. 2014 Apr;15(2):417-24.

Sodium glycerophosphate is one of several glycerophosphates. Clinically, it is used to treat or prevent hypophosphatemia. Glycerophosphate is hydrolyzed in vivo to inorganic phosphates and glycerol. The extent of this reaction depends on the activity of serum alkaline phosphatase. Sodium glycerophosphate is the sodium salt form of an organic phosphate compound that provides the phosphates required for nutrition. Furthermore, sodium glycerophosphate can be used as a phosphate diluent when the body is contaminated with the beta-ray radioisotope phosphate P-32 (P-32), as P-32 competes with phosphate for absorption. When large doses of sodium glycerophosphate are administered, P-32 absorption can be inhibited or minimized. See also: Anhydrous sodium glycerophosphate (note moved to).

---

Drug Indications Sodium glycerophosphate is indicated as a phosphate source in total parenteral nutrition. It is used in combination with amino acids, glucose, lipid emulsions, and other electrolytes.
FDA Label

---

Mechanism of Action Sodium glycerophosphate is used as a donor of inorganic phosphates. For information on the role of phosphates in the body, see [DB09413].

---

Pharmacodynamics
Sodium glycerophosphate provides inorganic phosphate through hydrolysis.

---

β-glycerophosphate disodium pentahydrate is a standard component of osteogenic differentiation mixtures (usually used in combination with dexamethasone and ascorbic acid, abbreviated as DAG) for pluripotent stem cells, particularly bone marrow stromal cells (BMSCs). [2]
Its main functions are dual: 1) It serves as a source of inorganic phosphate (Pi), which is incorporated into the mineral phase of bone in the form of hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂). 2) The released Pi acts as an intracellular signaling molecule, affecting the expression of osteogenic genes. [2]
A key concern highlighted in the literature is that β-glycerophosphate disodium pentahydrate can induce mineralization (dystrophic mineralization) in cells that have not truly undergone osteogenic differentiation, especially at high concentrations (≥2 mM). This highlights the importance of using specific analytical methods other than standard mineralization staining (Alizarin Red S, von Korsa stain) to confirm bone-specific mineralization when assessing osteogenic potential. [2]
The mechanism of its signal transduction is thought to be that Pi enters the cell and activates the ERK1/2 MAPK signaling pathway through phosphorylation. Activated phosphorylated ERK1/2 (P-ERK1/2) translocates to the cell nucleus and participates in the regulation of osteogenic gene expression. [2]
β-glycerophosphate disodium pentahydrate is a key component in the formation of injectable thermosensitive hydrogels. When it is mixed with chitosan in an acidic solution, a sol-gel transition occurs, forming a biodegradable gel in vivo. [4]
In this study, its main functions are: 1) to neutralize the acidic chitosan solution and raise the pH value to about 6.9 (within the tumor pH range), thereby achieving thermosensitive gelation. 2) As a gelling agent, its concentration (and chitosan concentration) directly affects the gelation time (the higher the concentration, the shorter the gelation time). [4]
C/GP hydrogel systems containing β-glycerophosphate disodium pentahydrate can be used as sustained-release carriers for the hydrophobic anticancer drug docetaxel (DTX) without the need for toxic solvents such as polysorbate 80. [4]
This formulation showed controlled drug release, enhanced local tumor drug retention, and reduced systemic distribution in a mouse model of hepatocellular carcinoma (H22), thereby improving antitumor efficacy and reducing toxicity. [4]

C3H7NA2O6P

216.0374

233.988

13408-09-8

β-Glycerophosphate disodium salt hydrate;154804-51-0

22251426

White to yellow solid powder

488.2ºC at 760mmHg

>300ºC

249.1ºC

0.284

3

7

3

13

117

0

OFNNKPAERNWEDD-UHFFFAOYSA-L

InChI=1S/C3H9O6P.2Na.H2O/c4-1-3(5)2-9-10(6,7)8;;;/h3-5H,1-2H2,(H2,6,7,8);;;1H2/q;2*+1;/p-2

disodium;2,3-dihydroxypropyl phosphate;hydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~83.33 mg/mL (~272.22 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 100 mg/mL (326.68 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)