BHB, promote osteoblast proliferation, also for osteoblast differentiation

Published: admin | Format: 2017-02-27

β-Hydroxybutyrate

promote osteoblast proliferation, also for osteoblast differentiation

β-hydroxybutyric acid(BHB), is the mammalian body by the liver within the long-chain fatty acid metabolism generated as a major presence of ketone bodies in plasma and peripheral tissues. One level of plasma and tissue in the human body is normally maintained at around 0.1 mM. (Robinson, 1980) has long been recognized as one of the important energy metabolism and utilization intermediates in the body. (Müller, 1984) (Plecko, 2002). Because of their good penetrability and rapid diffusion to peripheral tissues, BHB improves tissue damage, protein metabolism, and metabolic disorders in these cases (Mackay, 1943).

1. A number of diseases, such as neurological disorders including epilepsy and myoclonus, and neurodegenerative diseases including Alzheimer's disease and dementia, which are benefited from increased ketone body levels, can be treated.

Previous studies have shown that 3HB can reduce the cell death of neuronal cell lines in human Alzheimer's and Parkinson's disease models. (Mackay, 1943) Increased levels of 3HB in plasma can improve cognitive function in elderly people with memory-related disorders such as Alzheimer's disease and Parkinson's disease. (Reger, 2004) In addition, 3HB has also been shown to improve epithelial cell damage by inhibiting apoptosis. (Nakamura, 2003)

2. Reduction of free radical damage by oxidative coenzyme Q (eg, ischemia);

The use of exogenous oral or injectable drugs for the treatment of diseases and injuries such as hemorrhagic shock (Katayama, 1994) (Hiraide, 1991), myocardial injury (Zou, 2002), extensive burns (Mizobata, 1996) and hypoxia, hypoxia, and sepsis (Suzuki, 2001).

3. Enhanced metabolic efficiency (increased training efficiency and motor performance, inadequate treatment of feeding, angina, myocardial infarction, etc.);

Another reported that BHB can correct the mitochondrial energy production defects, and estimated one by mitigation mitochondrial complex I, But by enhancing the oxidative phosphorylation of the substrate by the mitochondrial complex (succinate-ubiquinone oxidoreductase). (Tieu, 2003). All these evidences show a possible therapeutic effect on different diseases induced by stress. (Veech, 2001)

4. Treatment of brain cancer (such as astrocytoma) and other related diseases;

The results showed that BHB could promote cell proliferation in mammalian cells, such as fibroblasts and osteoblasts, suggesting that 3HB might have broad-spectrum growth-promoting effect on many kinds of cells. The results also showed that 3HB can induce the extracellular Ca2 + influx, causing the increase of intracellular calcium concentration, and calcium as the second messenger of cells and cell proliferation, differentiation, apoptosis, migration and other Cell physiological function is closely related. (Cheng, 2004)

5. For glucose metabolism disorders (such as type I diabetes, type II diabetes, low blood sugar and low ketosis, etc.) has a good effect. 3HB was found with the body energy metabolism disorders, diabetes and other major diseases are closely related.

 

Recent studies on the role of a pair of cells found that BHB can not only promote osteoblast proliferation, but also for osteoblast differentiation (such as alkaline phosphatase activity, the formation of calcified nodules, osteoblast differentiation index ) Have a certain stimulating effect. BHB can also inhibit the apoptosis of osteoblasts induced by serum-starved culture. This evidence strongly supports the role of BHB in the promotion of bone formation and suggests that BHB may have potential applications in bone repair and osteoporosis.

 

Ref:

Cheng S, Wu Q, Yang F, et al. Influence of DL-beta-hydroxybutyric acid on cell proliferation and calcium influx.[J]. Biomacromolecules, 2004, 6(2):593-7.

Hiraide A, Katayama M, Mizobata Y, et al. Effect of sodium D-3-hydroxybutyrate on amino acidemia in hemorrhagic hypotension.[J]. European Surgical Research.europäische Chirurgische Forschung.recherches Chirurgicales Européennes, 1991, 23(3-4):250-255.

Katayama M, Hiraide A, Sugimoto H, et al. Effect of ketone bodies on hyperglycemia and lactic acidemia in hemorrhagic stress.[J]. Journal of Parenteral and Enteral Nutrition, 1994, 18(5):442-6.

Mackay E M. The Significance of Ketosis[J]. Journal of Clinical Endocrinology & Metabolism, 1943, 3(2):101-110.

Mizobata Y, Hiraide A, Katayama M, et al. Oxidation of d (−)3-hydroxybutyrate administered to rats with extensive burns[J]. Surgery Today, 1996, 26(3):173-8.

Müller M J, Paschen U, Seitz H J. Effect of ketone bodies on glucose production and utilization in the miniature pig.[J]. Journal of Clinical Investigation, 1984, 74(1):249-61.

Nakamura S, Shibuya M, Saito Y, et al. Protective effect of D-beta-hydroxybutyrate on corneal epithelia in dry eye conditions through suppression of apoptosis.[J]. Investigative Ophthalmology & Visual Science, 2003, 44(11):4682-8.

Plecko B, Stoeckler-Ipsiroglu S, Schober E, et al. Oral β-Hydroxybutyrate Supplementation in Two Patients with Hyperinsulinemic Hypoglycemia: Monitoring of β-Hydroxybutyrate Levels in Blood and Cerebrospinal Fluid, and in the Brain by In Vivo Magnetic Resonance Spectroscopy[J]. Pediatric Research, 2002, 52(2):301-6.

Reger M A, Welsh R K, Watson G S, et al. The relationship between neuropsychological functioning and driving ability in dementia: a meta-analysis.[J]. Neuropsychology, 2004, 18(1):85-93.

Robinson A M, Williamson D H. Physiological roles of ketone bodies as substrates and signals in mammalian tissues.[J]. Physiological Reviews, 1980, 60(1):241-250.

Suzuki M, Suzuki M, Sato K, et al. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats.[J]. Japanese Journal of Pharmacology, 2001, 87(2):143-50.

Tieu K, Perier C, Caspersen C, et al. D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease[J]. Journal of Clinical Investigation, 2003, 112(6):892-901.

Veech R L, Chance B, Kashiwaya Y, et al. Ketone Bodies, Potential Therapeutic Uses[J]. IUBMB Life, 2001, 51(4):241–247.

Zou Z, Sasaguri S, Rajesh K G, et al. dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts.[J]. Ajp Heart & Circulatory Physiology, 2002, 283(5):1968-1974.

 


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