Dataset Information

Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.

ABSTRACT: A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age- and menopause-associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging- and ovariectomy (OVX)-induced bone-fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS-induced regulation of BMSC fate and bone-fat balance. γ-Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging- and OVX-induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS-induced regulation of osteocyte NPY.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8693044 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.

Zhang Yan Y Chen Chun-Yuan CY Liu Yi-Wei YW Rao Shan-Shan SS Tan Yi-Juan YJ Qian Yu-Xuan YX Xia Kun K Huang Jie J Liu Xi-Xi XX Hong Chun-Gu CG Yin Hao H Cao Jia J Feng Shi-Kai SK He Ze-Hui ZH Li You-You YY Luo Zhong-Wei ZW Wu Ben B Yan Zi-Qi ZQ Chen Tuan-Hui TH Chen Meng-Lu ML Wang Yi-Yi YY Wang Zhen-Xing ZX Liu Zheng-Zhao ZZ Luo Ming-Jie MJ Hu Xiong-Ke XK Jin Ling L Wan Teng-Fei TF Yue Tao T Tang Si-Yuan SY Xie Hui H

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20211031 24

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age- and menopause-associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging- and ovariecto ...[more]

PMID: 34719888

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Project description:BackgroundSkeletal aging is characterized by a decrease in bone mass and an increase in marrowfat content. Advanced oxidation protein products (AOPPs) accumulate easily with aging and disrupt redox homeostasis. We examined whether AOPPs accumulation contributes to the bone-fat imbalance during skeletal aging.MethodsBoth young and aged mice were employed to assess the changes of AOPPs levels and its contribution to bone-fat imbalance during skeletal aging. Primary bone marrow mesenchymal stromal cells (MSCs) were used to examine the potential role of AOPPs in age-related switch between osteogenic and adipogenic differentiation. Aged mice were also gavaged by non-selective antioxidant N-acetyl-L-cysteine (NAC), followed by close monitoring of the changes in AOPPs levels and bone-fat metabolism. Furthermore, young mice were chronically exposed to AOPPs and then evaluated for the changes of bone mass and marrow adiposity.ResultsThe levels of AOPPs in serum and bone marrow were markedly higher in aged mice than that in young mice. Age-related accumulation of AOPPs was accompanied by reduced bone formation, increased marrow adiposity and deterioration of bone microstructure. Reduced AOPPs accumulation by antioxidant NAC leaded to improvement of the bone-fat imbalance in aged mice. Similarly, the bone-fat imbalance was induced by chronic AOPPs loading in young mice. Compared with MSCs from young mice, MSCs from aged mice tended to differentiate into adipocytes rather than osteoblasts and displayed cellular senescence. Exposure of primary MSCs to AOPPs resulted in the switch from osteogenic to adipogenic lineage and cellular senescence. AOPPs challenge also increased intracellular ROS generation by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. The antioxidant NAC, after scavenging ROS, ameliorated the AOPPs-induced lineage switch and senescence in MSCs by inhibiting the PI3K/AKT/mTOR pathway.ConclusionOur findings revealed the involvement of AOPPs in age-related switch between osteogenic and adipogenic differentiation, and illuminated a novel potential mechanism underlying bone-fat imbalance during skeletal aging.The translational potential of this articleReducing AOPPs accumulation and its cascading effects on MSCs might be an attractive strategy for delaying skeletal aging.

Dataset Information

Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.

Publications

Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.

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