Disruption of the aldehyde dehydrogenase 2 gene increases the bone anabolic response to intermittent PTH treatment in an ovariectomized mouse model

Kosugi, Kenji; Tajima, Takafumi; Menuki, Kunitaka; Okuma, Kayoko Furukawa; Tokuda, Kotaro; Fukuda, Hokuto; Okada, Yasuaki; Tsukamoto, Manabu; Yamanaka, Yoshiaki; Zenke, Yukichi

doi:10.1016/j.bone.2020.115370

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…Mice were given low-(20 μg/kg) or high-(40 μg/kg) concentration recombinant human PTH; the mice were categorized into the low-concentration PTH (LPTH) group and the high-concentration PTH (HPTH) group, respectively. During the modelling, PTH was injected into the mice by subcutaneous injection at 10 : 00 daily [20].…”

Section: 2mentioning

confidence: 99%

Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB

Wei

et al. 2022

Oxidative Medicine and Cellular Longevity

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As an important hormone that regulates the balance of calcium and phosphorus, parathyroid hormone (PTH) has also been found to have an important function in intervertebral disc degeneration (IVDD). Our aim was to investigate the mechanism by which PTH alleviates IVDD. In this study, the PTH 1 receptor was found to be highly expressed in severely degenerated human nucleus pulposus (NP) cells. We found in the mouse model of IVDD that supplementation with exogenous PTH alleviated the narrowing of the intervertebral space and the degradation of the extracellular matrix (ECM) caused by tail suspension (TS). In addition, inflammation, oxidative stress, and apoptosis levels were significantly increased in the intervertebral disc tissues of TS-induced mice, and the activity of NP cells was decreased. TS also led to the downregulation of Sonic hedgehog (SHH) signalling pathway-related signal molecules in NP cells such as SHH, Smoothened, and GLI1. However, supplementation with exogenous PTH can reverse these changes. In vitro, PTH also promotes the activity of NP cells and the secretion of ECM. However, the antagonist of the SHH signalling pathway can inhibit the therapeutic effect of PTH on NP cells. In addition, a cAMP-response element-binding protein, as an important transcription factor, was found to mediate the promotion of PTH on the SHH signalling pathway. Our results revealed that PTH can alleviate IVDD by inhibiting inflammation, oxidative stress, and apoptosis and improving the activity of NP cells via activating the SHH signalling pathway.

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Section: 2mentioning

confidence: 99%

Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB

Wei

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The single nucleotide polymorphism of aldehyde dehydrogenase 2 (ALDH2) at rs671 loci correlates with osteoporosis development and osteoporotic hip fracture [ 35 ]. Mice lacking the Aldh2 gene show high bone mass phenotypes and increased responses to the bone anabolic actions of PTH treatment [ 36 ].…”

Section: The Role Of Mitochondrial Homeostasis In Bone-forming Cell Functionmentioning

confidence: 99%

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Wang

Chen

et al. 2021

Antioxidants

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Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

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Parathyroid hormone and its related peptides in bone metabolism

Chen

Wang

Hao

et al. 2021

Biochemical Pharmacology

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Disruption of the aldehyde dehydrogenase 2 gene increases the bone anabolic response to intermittent PTH treatment in an ovariectomized mouse model

Cited by 3 publications

References 51 publications

Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB

Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Parathyroid hormone and its related peptides in bone metabolism

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