The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone Resorption<i>In Vitro</i>

Zhai, Yuankun; Pan, Yuanjiang; Niu, Youguo; Li, Chenrui; Wu, Xuesong; Wu, Fan; Lu, Tingli; Mei, Qibing; Chen, Xian

doi:10.1155/2014/921954

Cited by 31 publications

(26 citation statements)

References 42 publications

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“…OCN is also used as a biomarker of skeletal development, and increased serum OCN level is associated with increased bone mineral density during osteoporosis treatment [48,49]. However, in our study, elevated OCN levels were accompanied by decreased BMD.…”

Section: Discussioncontrasting

confidence: 66%

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Zou

Xiong

Lai

et al. 2015

Sci. China Life Sci.

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Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice (PUG), a model of human X-linked hypophosphatemic rickets (XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus-and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin (OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients. glucose metabolism, mineral homeostasis, bone, Phex, X-linked hypophosphatemic rickets Citation:Zou JH, Xiong XW, Lai BB, Sun M, Tu X, Gao X. Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model. [5,6]. In the past decades, bone was studied as an endocrinal organ [7,8]. Interactions between bone and energy metabolism aroused extensive interests and concerns [911]. Phex is mainly expressed in osteoblasts and odontoblasts [1214] and its mutations lead to reduced 1,25-(OH) 2 D 3 and elevated circulating FGF23 (fibroblast growth factor 23) [1517]. 1,25-(OH) 2 D 3 and its receptor could influence expression of uncoupling protein (UCP) in adipocytes [18,19]. In vitro studies demonstrate that the role of 1,25-(OH) 2 D 3 in lipid metabolism is regulator of peroxisome proliferator-activated receptor alpha (Ppara) [20]. Circulating FGF23 is also associated with fat mass and serum lipids [21]. In mouse models of XLH, like Hyp mice, decreased renal glucose reabsorption activity [22], increased glucose production in renal proximal tubules [23] and osteoblasts [24] were observed. The only known physiological substrate of PHEX protein, acidic serine aspartate-rich MEPE associated motif (ASARM peptide), could regulate glucose metabolism and insulin signaling [14]. The above findings indicate PHEXmediated association between skeletal function and energy

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Section: Discussioncontrasting

confidence: 66%

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Zou

Xiong

Lai

et al. 2015

Sci. China Life Sci.

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“…The altered serum levels of CTX and osteocalcin were significantly reversed by treatment with mollugin. The activities of TRAP (marker for bone resorption) and ALP in osteoblasts are significantly altered in osteoporosis [15]. In this study, treatment with mollugin significantly reversed the altered activities of TRAP and ALP in osteoporotic rats.…”

Section: Discussionmentioning

confidence: 49%

Mollugin attenuates glucocorticoid-induced osteoporosis in rats via Akt/P13K pathway

Jia¹,

Gao²,

Wang³

et al. 2018

Trop. J. Pharm Res

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Purpose: To investigate the protective effect of mollugin on glucocorticoid (GC)-induced osteoporosis in rats. Methods: A total of 30 female Sprague Dawley rats (weighing 180 to 200 g) were randomly assigned to five groups of six rats each: control, GC and mollugin groups (20, 40 and 80 mg/kg, respectively). Except for the control group, osteoporosis was induced in the rats by intramuscular administration of dexamethasone at a dose of 2.5 mg/kg twice weekly for nine weeks. Bone mineral density (BMD) and serum activities of tartrate-resistant acid phosphatase (TRAP) and specific alkaline phosphatase (ALP), and levels of collagen type I fragment (CTX) and osteocalcin were estimated. The effect of mollugin alone, and in the presence of PI3K/Akt inhibitor on the proliferation of bone marrow osteoblasts was investigated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide (MTT) assay. Western blotting was used for determination of the expressions of p-Akt, Akt and cyclin D1 protein. Results: There were significant increases in body weights of rats in GC group, when compared with the control group. However, treatment with mollugin significantly reduced the body weights in a dosedependent manner (p < 0.05). The BMD was significantly reduced in GC group, relative to the control group (p < 0.05). Serum activities of TRAP and ALP were significantly higher in GC group than in control group, but were significantly reduced by mollugin treatment (p < 0.05). Serum level of CTX was significantly increased and osteocalcin reduced in the GC group, relative to control (p < 0.05). Osteoblast proliferation was significantly higher in the mollugin-treated groups. The expressions of p-Akt, Akt and cyclin D1 were significantly and dose-dependently higher in mollugin-treated groups (p < 0.05). There were more viable osteoblasts in the mollugin-treated groups than in the untreated group. However, treatment with mollugin in the presence of PI3K/Akt inhibitor significantly reduced their viability (p < 0.05). Conclusion: Mollugin has therapeutic potential for GC-induced osteoporosis via mechanism involving the PI3K/Akt pathway.

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“…30) Studies also showed that osthole attenuated intestinal, myocardial, and spinal cord ischemia-reperfusion injury in animal models. 31,32) Besides, osthole could effectively inhibit TGF-β1 expression in fibroblasts and protect against cardiac and hepatic fibrosis.…”

Section: )mentioning

confidence: 99%

Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis <i>via</i> Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1–7) Axis and Decreasing Inflammation Responses in Rats

Hao

Liu

2016

Biological & Pharmaceutical Bulletin

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Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

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The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone ResorptionIn Vitro

Cited by 31 publications

References 42 publications

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Mollugin attenuates glucocorticoid-induced osteoporosis in rats via Akt/P13K pathway

Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis <i>via</i> Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1–7) Axis and Decreasing Inflammation Responses in Rats

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