Since its discovery four decades ago as a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al

Since its discovery four decades ago as a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al., 1980; Wang et?al., 2011). but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-B), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials. two important mechanisms whereby it directly inhibits GSK3 by competition with magnesium ions and indirectly inhibits GSK3 serine phosphorylation (Eldar-Finkelman and Martinez, 2011). Since its discovery four decades ago as a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al., 1980; Wang et?al., 2011). For instance, GSK3 plays a functional role in Wingless (Wnt)/beta ()-catenin, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappa B (NF-B) signaling pathways (Wang et?al., 2011). Intriguingly, these transmission transduction pathways have been implicated in the regulation of bone metabolism and homeostasis thus suggesting the concept of lithium as a potential osteoprotective agent. The purpose of the current evaluate is to provide data showing the bone-protecting effects of lithium in animals and humans. The potential mechanisms of action underlying its bone-sparing effects are also explained. We hope to provide an overview of the effectiveness and efficacy of lithium against bone-related disorders to encourage its greater use of lithium apart from the established anti-manic property. Evidence Acquisition The literature search was performed from November 15, 2019 until December 15, 2019 with PubMed and Medline electronic databases using query string lithium AND (bone OR osteoporosis OR fracture OR osteoblast OR osteoclast OR osteocyte). The titles and abstracts were screened and relevant full-text articles were retrieved. A total of 40 initial research articles inclusive of preclinical experimental evidence and human epidemiological data were included in this review. Effects of Lithium on Bone: Evidence From Studies The effects of lithium on bone have been widely established in various types of animals, including rodents, goats, rabbits, dogs, and chickens. The models utilised by investigators vary between studies, including the use of animals subjected to surgical castration, chemical castration, bone defects, and/or fractures, genetically senescence animals, knockout animals, as well as normal healthy animals ( Table 1 ). Table 1 Effects of lithium on bone study, a bone defect (5 mm in length, 1.5 mm in width and 1 mm in depth) was made 6 mm below the knee joint of male Wistar rats and filled with BD Matrigel? basement membrane matrix with lithium carbonate (Li2CO3, 10 mM) for 14 days. Micro-computed tomography (Micro-CT) analysis and bone histomorphometry were performed in the intracortical- and the endocortical-formation area. The osteoclast number (Oc.N) was significantly decreased but the percentage of lamellar BV was significantly increased, reiterating the acceleration of bone regeneration in promoting high-intensity bone formation (Arioka et?al., 2014). In adult male goats, a symmetrical 10 mm round bone defect was launched to the tibial facies medialis and the defect was filled with lithium-incorporated deproteinized bovine bone (Li-DBB) scaffold. Qualitatively, it was found that callus was created in the defect region with dense and normal morphology of trabeculae in the Li-DBB group after 12 weeks. Quantitatively, it was noted that this mean gray values, mean pixel value, calcified callus BV, trabecular thickness (Tb.Th) and mean osteogenic area were significantly higher in bone defects filled with Li-DBB scaffold compared to those filled with deproteinized bovine bone (DBB) scaffold without lithium (Guo et?al., 2018). In the same year, Li et?al. (2018) examined the bone defect repairing effects of nano-lithium-hydroxyapatite (Li-nHA) scaffold in glucocorticoid-induced osteonecrosis of the femoral head Adrafinil in adult male Japanese white rabbits. Briefly, the rabbits were intravenously injected with lipopolysaccharide (LPS) followed by three intramuscularly injections of methylprednisolone acetate (20 mg/kg, time interval of 24 hours) into the right gluteus medius muscle after 24 hours. The femoral head defect was created and filled with Li-nHA scaffold. Micro-CT analysis showed that the.(2005), LiCl was gavage-fed to three different strains of 8-week-old mice [low-density lipoprotein receptor-related protein 5 (Lrp5)-knockout (evidence suggests the promising osteoprotective effects of lithium in defective bones and osteoporotic condition. it directly inhibits GSK3 by competition with magnesium ions and indirectly inhibits GSK3 serine phosphorylation PRL (Eldar-Finkelman and Martinez, 2011). Since its discovery four decades ago as a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al., 1980; Wang et?al., 2011). For instance, GSK3 plays a functional role in Wingless (Wnt)/beta ()-catenin, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappa B (NF-B) signaling pathways (Wang et?al., 2011). Intriguingly, these signal transduction pathways have been implicated in the regulation of bone metabolism and homeostasis thus suggesting the concept of lithium as a potential osteoprotective agent. The purpose of the current review is to provide data showing the bone-protecting effects of lithium in animals and humans. The potential mechanisms of action underlying its bone-sparing effects are also described. We hope to provide an overview of the effectiveness and efficacy of lithium against bone-related disorders to encourage its greater use of lithium apart from the established anti-manic property. Evidence Acquisition The literature search was performed from November 15, 2019 until December 15, 2019 with PubMed and Medline electronic databases using query string lithium AND (bone OR osteoporosis OR fracture OR osteoblast OR osteoclast OR osteocyte). The titles and abstracts were screened and relevant full-text articles were retrieved. A total of 40 original research articles inclusive of preclinical experimental evidence and human epidemiological data were included in this review. Effects of Lithium on Bone: Evidence From Studies The effects of lithium on bone have been widely established in various types of animals, including rodents, goats, rabbits, dogs, Adrafinil and chickens. The models utilised by investigators vary between studies, including the use of animals subjected to surgical castration, chemical castration, bone defects, and/or fractures, genetically senescence animals, knockout animals, as well as normal healthy animals ( Table 1 ). Table 1 Effects of lithium on bone study, a bone defect (5 mm in length, 1.5 mm in width and 1 mm in depth) was made 6 mm below the knee joint of male Wistar rats and filled with BD Matrigel? basement membrane matrix with lithium carbonate (Li2CO3, 10 mM) for 14 days. Micro-computed tomography (Micro-CT) analysis and bone histomorphometry were performed in the intracortical- and the endocortical-formation area. The osteoclast number (Oc.N) was significantly decreased but the percentage of lamellar BV was significantly increased, reiterating the acceleration of bone regeneration in promoting high-intensity bone formation (Arioka et?al., 2014). In adult male goats, a symmetrical 10 mm round bone defect was introduced to the tibial facies medialis and the defect was filled with lithium-incorporated deproteinized bovine bone (Li-DBB) scaffold. Qualitatively, it was found that callus was formed in the defect region with dense and normal morphology of trabeculae in the Li-DBB group after 12 weeks. Quantitatively, it was noted that the mean gray values, mean pixel value, calcified callus BV, trabecular thickness (Tb.Th) and mean osteogenic area were significantly higher in bone defects filled with Li-DBB scaffold compared to those filled with deproteinized bovine bone (DBB) scaffold without lithium (Guo et?al., 2018). In the same year, Li et?al. (2018) examined the bone defect repairing effects of nano-lithium-hydroxyapatite (Li-nHA) scaffold in glucocorticoid-induced osteonecrosis of the femoral head in adult male Japanese white.The co-cultures of bone marrow MSCs and Li-nHA had lower expression of GSK3 and peroxisome proliferator-activated receptor-gamma (PPAR-) but higher expression of -catenin (Li et?al., 2018). but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-B), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials. two important mechanisms whereby it directly inhibits GSK3 by competition with magnesium ions and indirectly inhibits GSK3 serine phosphorylation (Eldar-Finkelman and Martinez, 2011). Since its discovery four decades ago as a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al., 1980; Wang et?al., 2011). For instance, GSK3 plays a functional role in Wingless (Wnt)/beta ()-catenin, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappa B (NF-B) signaling pathways (Wang et?al., 2011). Intriguingly, these signal transduction pathways have been implicated in the regulation of bone metabolism and homeostasis thus suggesting the concept of lithium as a potential osteoprotective agent. The purpose of the current review is to provide data showing the bone-protecting effects of lithium in animals and humans. The potential mechanisms of action underlying its bone-sparing effects are also described. We hope to provide an overview of the effectiveness and efficacy of lithium against bone-related disorders to encourage its greater use of lithium apart from the established anti-manic property. Evidence Acquisition The literature search was performed from November 15, 2019 until December 15, 2019 with PubMed and Medline electronic databases using query string lithium AND (bone OR osteoporosis OR fracture OR osteoblast OR osteoclast OR osteocyte). The titles and abstracts were screened and relevant full-text articles were retrieved. A total of 40 original research articles inclusive of preclinical experimental evidence and human epidemiological data were included in this review. Effects of Lithium on Bone: Evidence From Studies The effects of lithium on bone have been widely founded in various types of animals, including rodents, goats, rabbits, dogs, and chickens. The models utilised by investigators vary between studies, including the use of animals subjected to medical castration, chemical castration, bone problems, and/or fractures, genetically senescence animals, knockout animals, as well as normal healthy animals ( Table 1 ). Table 1 Effects of lithium on bone study, a bone defect (5 mm in length, 1.5 mm in width and 1 mm in depth) was made 6 mm below the knee joint of male Wistar rats and filled with BD Matrigel? basement membrane matrix with lithium carbonate (Li2CO3, 10 mM) for 14 days. Micro-computed tomography (Micro-CT) analysis and bone histomorphometry were performed in the intracortical- and the endocortical-formation area. The osteoclast quantity (Oc.N) was significantly decreased but the percentage of lamellar BV was significantly increased, reiterating the acceleration of bone regeneration in promoting high-intensity bone formation (Arioka et?al., 2014). In adult male goats, a symmetrical 10 mm round bone defect was launched to the tibial facies medialis and the defect was filled with lithium-incorporated deproteinized bovine bone (Li-DBB) scaffold. Qualitatively, it was found that callus was created in the defect region with dense and normal morphology of trabeculae in the Li-DBB group after 12 weeks. Quantitatively, it was noted the mean gray ideals, mean pixel value, calcified callus BV, trabecular thickness (Tb.Th) and mean osteogenic area were significantly higher in bone defects filled with Li-DBB scaffold compared to those filled with deproteinized bovine bone (DBB) scaffold without lithium (Guo et?al., 2018). In the same yr, Li et?al. (2018) examined the bone defect repairing effects of nano-lithium-hydroxyapatite (Li-nHA) scaffold in glucocorticoid-induced osteonecrosis of the femoral head in adult male Japanese white rabbits. Briefly, the rabbits were intravenously injected with lipopolysaccharide (LPS) followed by three intramuscularly injections of methylprednisolone acetate (20 mg/kg, time interval of 24 hours) into the right gluteus medius muscle mass after 24 hours. The femoral head defect was created and packed. Western blot results also exposed that titanium particle activation significantly improved ERK and p38 MAPK phosphorylation. pathways but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-B), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers safety to the skeleton but its medical utility awaits further validation from human being medical trials. two important mechanisms whereby it directly inhibits GSK3 by competition with magnesium ions and indirectly inhibits GSK3 serine phosphorylation (Eldar-Finkelman and Martinez, 2011). Since its finding four decades ago like a protein kinase that phosphorylates and inhibits glycogen synthase, GSK3 has been demonstrated to be a point of convergence for multiple cell signaling pathways involved in physiological processes (Embi et?al., 1980; Wang et?al., 2011). For instance, GSK3 plays a functional part in Wingless (Wnt)/beta ()-catenin, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappa B (NF-B) signaling pathways (Wang et?al., 2011). Intriguingly, these transmission transduction pathways have been implicated in the rules of bone rate of metabolism and homeostasis therefore suggesting the concept of lithium like a potential osteoprotective agent. The purpose of the current evaluate is to provide data showing the bone-protecting effects of lithium in animals and humans. The potential mechanisms of action underlying its bone-sparing effects are also explained. We hope to provide an overview of the performance and effectiveness of lithium against bone-related disorders to encourage its greater use of lithium apart from the founded anti-manic property. Evidence Acquisition The literature search was performed from November 15, 2019 until December 15, 2019 with PubMed and Medline electronic databases using query string lithium AND (bone OR osteoporosis OR fracture OR osteoblast OR osteoclast OR osteocyte). The titles and abstracts were screened and relevant full-text content articles were retrieved. A total of 40 unique research articles inclusive of preclinical experimental evidence and human being epidemiological data were included in this review. Effects of Lithium on Bone: Evidence From Studies The effects of lithium on bone have been widely founded in various types of animals, including rodents, goats, rabbits, dogs, and chickens. The models utilised by investigators vary between studies, including the use of animals subjected to medical castration, chemical castration, bone problems, and/or fractures, genetically senescence animals, knockout animals, as well as normal healthy animals ( Desk 1 ). Desk 1 Ramifications of lithium on bone tissue study, a bone tissue defect (5 mm long, 1.5 mm wide and 1 mm comprehensive) was produced 6 mm below the knee joint of male Wistar rats and filled up with BD Matrigel? cellar membrane matrix with lithium carbonate (Li2CO3, 10 mM) for two weeks. Micro-computed tomography (Micro-CT) evaluation and bone tissue histomorphometry had been performed in the intracortical- as well as the endocortical-formation region. The osteoclast amount (Oc.N) was significantly decreased however the percentage of lamellar BV was significantly increased, reiterating the acceleration of bone tissue regeneration to advertise high-intensity bone tissue development (Arioka et?al., 2014). In adult man goats, a symmetrical 10 mm around bone tissue defect was presented towards the tibial facies medialis as well as the defect was filled up with lithium-incorporated deproteinized bovine bone tissue (Li-DBB) scaffold. Qualitatively, it had been discovered that callus was produced in the defect area with thick and regular morphology of trabeculae in the Li-DBB group after 12 weeks. Quantitatively, it had been noted which the mean gray beliefs, mean pixel worth, calcified callus BV, trabecular width (Tb.Th) and mean osteogenic region were considerably higher in bone tissue defects filled up with Li-DBB scaffold in comparison to those filled up with deproteinized bovine bone tissue (DBB) scaffold without lithium (Guo et?al., 2018). In the same calendar year, Li et?al. (2018) analyzed the bone tissue defect repairing ramifications of nano-lithium-hydroxyapatite (Li-nHA) scaffold in glucocorticoid-induced osteonecrosis from the femoral mind in adult man Japanese white rabbits. Quickly, the rabbits had been intravenously injected with lipopolysaccharide (LPS) accompanied by three intramuscularly shots of methylprednisolone acetate (20 mg/kg, period interval of a day) in to the correct gluteus medius muscles after a day. The femoral mind defect was made and filled up with Li-nHA scaffold. Micro-CT evaluation showed which the Li-nHA group demonstrated moderate defect fix, confirmed with the quantitative evaluation portrayed as higher Adrafinil beliefs of bone tissue volume and bone relative density when compared with the controls. Results from histological recognition also showed which the Li-nHA group provided a larger brand-new bone tissue region compared to the control pets (Li et?al., 2018). Recently, lithium-doped calcium mineral polyphosphate (Li-CPP) was.