Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice

Weske, Sarah; Vaidya, Mithila; Lipinski, Karin von Wnuck; Keul, Petra; Manthe, Kristina; Burkhart, Christoph; Haberhauer, Gebhard; Heusch, Gerd; Levkau, Bodo

doi:10.1016/j.bone.2019.04.015

Cited by 22 publications

(21 citation statements)

References 38 publications

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“…It has been revealed that blocking S1P lyase can increase S1P levels and stimulate the differentiation of osteoblasts through S1PR2 in mouse osteoporosis models (48,49). Weske et al further showed that increasing the level of S1P by inhibiting S1P lyase enhanced bone formation and potently stimulated osteoblastogenesis by inducing adipogenesis and inhibited osteoclastogenesis by inducing osteoprotegerin production (50).…”

Section: Therapeutic Role Of S1p In Osteoporosismentioning

confidence: 99%

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects—a narrative review

Tian

Ma²,

Xie

et al. 2021

Ann Palliat Med

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Sphingosine 1-phosphate (S1P) regulates many cellular functions, such as differentiation, proliferation, migration, morphogenesis, cytoskeletal organization, adhesion, tight junction assembly, apoptosis and the localization of different cell types. S1P also controls the migration of osteoclast precursors between the blood and bone, and it keeps osteoclast precursors away from bone surfaces to reduce bone degradation, thus preventing bone decay. Osteoporosis is a systemic bone disease that predisposes patients to bone fracture due to decreased bone density and quality, disrupted bone microarchitecture, and increased bone fragility. As the global elderly population increases, the incidence of osteoporosis will greatly increase, and the associated adverse consequences will become more serious. S1P plays an important role in homeostasis, and disruption of the balance between osteoblasts and osteoclasts may induce osteoporosis.A high frequency of osteoporotic fracture is associated with increased plasma S1P levels. Studies have shown that S1P is an important therapeutic target in osteoporosis because it controls the migration of osteoclast precursors, vigorously maintains the bone mineralization process, and is a critical regulator of osteoclastogenesis. Improved understanding of the functional roles and molecular mechanisms of S1P in bone turnover could facilitate the discovery of novel targets for the treatment of osteoporosis. This review provides a critical discussion of the role of S1P in osteoporosis and treatments.

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Section: Therapeutic Role Of S1p In Osteoporosismentioning

confidence: 99%

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects—a narrative review

Tian

Ma²,

Xie

et al. 2021

Ann Palliat Med

View full text Add to dashboard Cite

show abstract

“…However, inhibition of S1P degradation increases the S1P concentration, resulting in the enhancement of all S1P receptor signals. As such, it has been pointed out that lymphocytic cytopenia may occur as a side effect [ 18 ]. Meanwhile, when S1PR2 agonist (CYM-5520) was applied to a mouse osteoporosis model by ovariectomy, lymphopenia as seen in LX2931 was not observed, and a comparative increase in bone mass and osteoblast number as LX2931 was observed [ 18 ].…”

Section: Function Of S1p Signaling Pathway In Bone Tissuementioning

confidence: 99%

“…As such, it has been pointed out that lymphocytic cytopenia may occur as a side effect [ 18 ]. Meanwhile, when S1PR2 agonist (CYM-5520) was applied to a mouse osteoporosis model by ovariectomy, lymphopenia as seen in LX2931 was not observed, and a comparative increase in bone mass and osteoblast number as LX2931 was observed [ 18 ]. From the above, it was suggested that the bone anabolic effect of the drug targeting S1PR2 would be a useful treatment method for osteoporosis-related diseases.…”

Section: Function Of S1p Signaling Pathway In Bone Tissuementioning

confidence: 99%

“…Therefore, selective agonists of S1PR1 and S1PR2 might be useful for clinical application. As mentioned above, the bone anabolic effect of selective S1PR2 agonist [ 18 ] would be a useful treatment method for osteoporosis. In multiple sclerosis, in addition to FTY720, selective S1PR1 agonists or S1P receptor drugs without serious adverse events have been developed, and a number of clinical trials are undergoing [ 8 ].…”

Section: Current State Of S1p In Endodontics and Challenges For Regenmentioning

confidence: 99%

“…In recent years, considerable progress has been made to elucidate the role of S1P signaling pathway in bone tissues. Currently, research efforts are underway to study the following mechanisms: osteoclast differentiation inhibitory effect by osteoclast progenitor cell migration control via S1PR1 [ 9 ]; osteoblast differentiation promoting effect [ [10] , [11] , [12] , [13] ] and bone formation [ [11] , [12] , [13] , [14] ] via S1PR1, S1PR2, and S1PR3; and osteoporosis treatment through S1PR2 regulation by osteoclasts and osteoblasts [ [15] , [16] , [17] , [18] ]. Additionally, S1P regulates both the promotion of osteoblastogenesis and the inhibition of adipogenesis in C3H10T1/2 cells, which are functionally similar to mesenchymal stem cells [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dental regenerative therapy targeting sphingosine-1-phosphate (S1P) signaling pathway in endodontics

Matsuzaki

Minakami

Matsumoto

et al. 2020

Japanese Dental Science Review

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The establishment of regenerative therapy in endodontics targeting the dentin-pulp complex, cementum, periodontal ligament tissue, and alveolar bone will provide valuable information to preserve teeth. It is well known that the application of stem cells such as induced pluripotent stem cells, embryonic stem cells, and somatic stem cells is effective in regenerative medicine. There are many somatic stem cells in teeth and periodontal tissues including dental pulp stem cells (DPSCs), stem cells from the apical papilla, and periodontal ligament stem cells. Particularly, several studies have reported the regeneration of clinical pulp tissue and alveolar bone by DPSCs transplantation. However, further scientific issues for practical implementation remain to be addressed. Sphingosine-1-phosphate (S1P) acts as a bioactive signaling molecule that has multiple biological functions including cellular differentiation, and has been shown to be responsible for bone resorption and formation. Here we discuss a strategy for bone regeneration and a possibility for regenerative endodontics targeting S1P signaling pathway as one of approaches for induction of regeneration by improving the regenerative capacity of endogenous cells. Scientific field of dental science Endodontology

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Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities

Blaho

2020

Druggable Lipid Signaling Pathways

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Intensive research in the field of sphingolipids has revealed diverse roles in cell biological responses and human health and disease. This immense molecular family is primarily represented by the bioactive molecules ceramide, sphingosine, and sphingosine 1-phosphate (S1P). The flux of sphingolipid metabolism at both the subcellular and extracellular levels provides multiple opportunities for pharmacological intervention. The caveat is that perturbation of any single node of this highly regulated flux may have effects that propagate throughout the metabolic network in a dramatic and sometimes unexpected manner. Beginning with S1P, the receptors for which have thus far been the most clinically tractable pharmacological targets, this review will describe recent advances in therapeutic modulators targeting sphingolipids, their chaperones, transporters, and metabolic enzymes.

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Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice

Cited by 22 publications

References 38 publications

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects—a narrative review

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects—a narrative review

Dental regenerative therapy targeting sphingosine-1-phosphate (S1P) signaling pathway in endodontics

Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities

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