Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R

Liu, Shuangxin; Zhu, Weiping; Li, Sijia; Ma, Jianchao; Zhang, Huitao; Li, Zhonghe; Zhang, Li; Zhang, Bin; Li, Zhuo; Liang, Xinling; Shi, Wei

doi:10.3892/ijmm.2015.2423

Cited by 21 publications

(15 citation statements)

References 44 publications

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“…Studies that were done on current treatments of osteoporosis such at BMP2 and PTH showed that long-term usage of these compounds resulted in enhancing osteoclast differentiation and bone resorption [7,29,30]. It could be speculated that long term treatment of osteoporosis using BMP2 and PTH might increase osteoclast differentiation and bone resorption due to the direct and indirect effects (via osteoblasts) on osteoclasts.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Nguyen¹,

Weidner²,

Schell³

et al. 2018

J Bone Marrow Res

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Background: Osteoporosis is a silent disease caused by low bone mineral density that results in bone fractures in 1 out of 2 women and 1 in 4 men over the age of 50. Although several treatments for osteopenia and osteoporosis are available, they have severe side effects and new treatments are desperately needed. Current treatments usually target osteoclasts and inhibit their activity or differentiation. Treatments that decrease osteoclast differentiation and activity but enhance osteogenesis and osteoblast activity are not available. We recently developed a peptide, CK2.3, that induces bone formation and increases bone mineral density as demonstrated by injection over the calvaria of 6 to 9-day-old mice and tail vein injection of 8-week-old mice. CK2.3 also decreased osteoclast formation and activity. However, these studies raise questions: does CK2.3 induce similar results in old mice and if so, what is the effective CK2.3 concentration and, is the bone mineral density of vertebrae of the spinal column increased as well? Methods: CK2.3 was systematically injected into the tail vein of female 6-month old mice with various concentrations of CK2.3: 0.76 μg/kg, 2.3 μg/kg, or 6.9 μg/kg per mice. Mice were sacrificed one week, two weeks, and four weeks after the first injection. Their spines and femurs were collected and analyzed for bone formation. Results: Femur and lumbar spine analyses found increased bone mineral density (BMD) and mineral apposition rate, with greater stiffness observed in femoral samples four weeks after the first injection. Histochemistry showed that osteoclastogenesis was suppressed in CK2.3 treated senile mice. Conclusions: For the first time, this study showed the increase of lumbar spine BMD by CK2.3. Moreover, it showed that enhancement of femur BMD was accompanied by increased femur stiffness only at medium concentration of CK2.3 four weeks after the first injection indicating the maintenance of bone’s structural integrity by CK2.3.

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Section: Discussionmentioning

confidence: 99%

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Nguyen¹,

Weidner²,

Schell³

et al. 2018

J Bone Marrow Res

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“…The prevailing scientific opinion is that only osteoblast-lineage cells possess a PTH receptor, with only a small number of researchers reporting that they are also present on osteoclast-lineage cells. Therefore, this raised osteoclast activity is not through direct action of PTH, but rather an indirect response to altered osteoblast function as continuous PTH raises RANKL and lowers OPG expression, increasing the RANKL:OPG ratio (Dempster et al, 2005 ; O'Brien et al, 2008 ; Silva and Bilezikian, 2015 ; Liu et al, 2016 ).…”

Section: Modulators Of Remodellingmentioning

confidence: 99%

In vitro Models of Bone Remodelling and Associated Disorders

Owen

Reilly

2018

Front. Bioeng. Biotechnol.

159

128

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Disruption of bone remodelling by diseases such as osteoporosis results in an imbalance between bone formation by osteoblasts and resorption by osteoclasts. Research into these metabolic bone disorders is primarily performed in vivo; however, in the last decade there has been increased interest in generating in vitro models that can reduce or replace our reliance on animal testing. With recent advances in biomaterials and tissue engineering the feasibility of laboratory-based alternatives is growing; however, to date there are no established in vitro models of bone remodelling. In vivo, remodelling is performed by organised packets of osteoblasts and osteoclasts called bone multicellular units (BMUs). The key determinant of whether osteoclasts form and remodelling occurs is the ratio between RANKL, a cytokine which stimulates osteoclastogenesis, and OPG, its inhibitor. This review initially details the different circumstances, conditions, and factors which have been found to modulate the RANKL:OPG ratio, and fundamental factors to be considered if a robust in vitro model is to be developed. Following this, an examination of what has been achieved thus far in replicating remodelling in vitro using three-dimensional co-cultures is performed, before overviewing how such systems are already being utilised in the study of associated diseases, such as metastatic cancer and dental disorders. Finally, a discussion of the most important considerations to be incorporated going forward is presented. This details the need for the use of cells capable of endogenously producing the required cytokines, application of mechanical stimulation, and the presence of appropriate hormones in order to produce a robust model of bone remodelling.

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“…In vivo studies have demonstrated that continuous infusion of PTH triggers a decrease of OPG and an increase of RANKL capable of inducing osteoclast differentiation and promoting bone resorption (Ma et al). Another reason for our results would be the increased expression of a3 and d2 subunits of vacuolar-type H + adenosine triphosphatase (V-ATPase), which accelerates intracellular acidification when activated and increases bone resorption capability of osteoclasts (Liu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Modulation of in vitro Osteoclast Activity Mediated by Different Doses of Parathyroid Hormone

et al. 2017

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SUMMARY:Bone remodeling is a process regulated by the interaction between cells and various molecules such as parathyroid hormone (PTH). The aim of the study was to evaluate the effect of different doses of PTH on osteoclast activity in a culture model of bone organs. Six-day-old male C57BL/6 mice (n=14) were euthanized and the calvariae were dissected and sectioned in the middle, keeping the periosteal and endosteal. The bone fragments were divided into three groups: Group I (control -without adding PTH), Group II (addition of 3 nM PTH) and Group III (30 nM PTH), all cultured in aMEM for up to 72 h osteoclast activity was evaluated by biochemical quantification of calcium released in the culture medium at intervals of 24, 48, and 72 h and by histomorphometric analysis of bone resorption lacunae at 72 h our results show that group II exhibited significantly higher values of calcium levels in the medium compared to group I (p<0.05) in all intervals, also being higher for group III at 24 hours (p<0.05). Group II promoted a greater demineralization area (22068 ± 2193 mm 2 ) than those found in group I (2084 ± 38 mm 2 ) and group III (8952 ± 246 mm 2 ), with statistically significant difference (p<0.001) among all groups. We concluded that in culture model of bone organs PTH promotes higher bone resorption when administered in lower doses.

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Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R

Cited by 21 publications

References 44 publications

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

In vitro Models of Bone Remodelling and Associated Disorders

Modulation of in vitro Osteoclast Activity Mediated by Different Doses of Parathyroid Hormone

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