Osteopontin - The stirring multifunctional regulatory factor in multisystem aging

Du, Yi; Mao, Liwei; Wang, Zhikun; Yang, Kai; Zhang, Lingli; Zou, Jun

doi:10.3389/fendo.2022.1014853

Cited by 16 publications

(7 citation statements)

References 150 publications

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“…Moreover, OPN plays an important role in the metabolic processes of organs and tissues, contributing to aging. 86 In patients with NAFLD/ NASH, OPN is abundantly expressed in the liver and activates hedgehog signaling, promoting liver fibrosis. 87 Genetically, OPN-deficient mice exhibit reduced triglyceride synthesis, preventing obesity-induced hepatic steatosis.…”

Section: Osteopontin (Opn)mentioning

confidence: 99%

The Regulation of Bone Metabolism by the Liver

Luo,

Zhang,

et al. 2024

Nature Cell and Science

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Chronic liver diseases and osteoporosis, seemingly unrelated diseases that occur with advanced age, are involved in different mechanisms contributing to liver and bone metabolic disorders. Secondary osteoporosis and increased bone fragility are common complications in patients with chronic liver disease, including common liver diseases such as nonalcoholic fatty liver disease, alcoholic fatty liver disease, and cholestatic hepatitis. Despite these associations, the intricate link between the liver and bones remains ambiguous. Here, we review the current molecules involved in liver-bone communication in three aspects: metabolic factors in the liver, hepatic modifying enzymes, and pro-inflammatory factors affected by liver and bone metabolism. The emphasis is on delineating the regulation of bone metabolism by the liver, with the aim of elucidating the intricate interplay between hepatic and bone metabolic processes. This exploration not only contributes to a better understanding of the dynamic relationship between the liver and bone but also lays the groundwork for more comprehensive therapeutic strategies targeting osteoporosis in patients with advanced chronic liver disease.

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Section: Osteopontin (Opn)mentioning

confidence: 99%

The Regulation of Bone Metabolism by the Liver

Luo,

Zhang,

et al. 2024

Nature Cell and Science

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“…OPN is involved in the aging process of many systems, including central nervous system aging [ 108 ]. Alzheimer’s disease (AD) is characterized by synaptic loss, which may be caused by dysfunction of microglial phagocytosis and complement activation [ 109 ].…”

Section: Immunoregulatory Roles Of Opn In Diseasesmentioning

confidence: 99%

Immunoregulatory Roles of Osteopontin in Diseases

Wang,

Niu

2024

Nutrients

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Osteopontin (OPN) is a multifunctional protein that plays a pivotal role in the immune system. It is involved in various biological processes, including cell adhesion, migration and survival. The study of the immunomodulatory effects of OPN is of paramount importance due to its potential therapeutic applications. A comprehensive understanding of how OPN regulates the immune response could pave the way for the development of novel treatments for a multitude of diseases, including autoimmune disorders, infectious diseases and cancer. Therefore, in the following paper, we provide a systematic overview of OPN and its immunoregulatory roles in various diseases, laying the foundation for the development of OPN-based therapies in the future.

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“…3 ). For instance, the osteopontin protein can (i) induce myofibroblast differentiation and promote fibrosis, (ii) control immunosuppression in tumors, and (iii) elicit many of the degenerative processes associated with aging and age-related diseases [ 222 , 223 ]. To conclude, there is convincing evidence that enhancers of the aging process stimulate the differentiation of myofibroblasts and thus promote fibrosis both in aging tissues and age-related diseases.…”

Section: Are Immunosuppressive Myofibroblasts Promoting the Aging Pro...mentioning

confidence: 99%

The role of immunosuppressive myofibroblasts in the aging process and age-related diseases

Salminen

2023

J Mol Med

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Tissue-resident fibroblasts are mesenchymal cells which control the structural integrity of the extracellular matrix (ECM). Fibroblasts possess a remarkable plasticity to allow them to adapt to the changes in the microenvironment and thus maintain tissue homeostasis. Several stresses, also those associated with the aging process, convert quiescent fibroblasts into myofibroblasts which not only display fibrogenic properties but also act as immune regulators cooperating both with tissue-resident immune cells and those immune cells recruited into affected tissues. TGF-β cytokine and reactive oxygen species (ROS) are major inducers of myofibroblast differentiation in pathological conditions either from quiescent fibroblasts or via transdifferentiation from certain other cell types, e.g., macrophages, adipocytes, pericytes, and endothelial cells. Intriguingly, TGF-β and ROS are also important signaling mediators between immunosuppressive cells, such as MDSCs, Tregs, and M2 macrophages. It seems that in pathological states, myofibroblasts are able to interact with the immunosuppressive network. There is clear evidence that a low-grade chronic inflammatory state in aging tissues is counteracted by activation of compensatory immunosuppression. Interestingly, common enhancers of the aging process, such as oxidative stress, loss of DNA integrity, and inflammatory insults, are inducers of myofibroblasts, whereas anti-aging treatments with metformin and rapamycin suppress the differentiation of myofibroblasts and thus prevent age-related tissue fibrosis. I will examine the reciprocal interactions between myofibroblasts and immunosuppressive cells within aging tissues. It seems that the differentiation of myofibroblasts with age-related harmful stresses enhances the activity of the immunosuppressive network which promotes tissue fibrosis and degeneration in elderly individuals.

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Osteopontin - The stirring multifunctional regulatory factor in multisystem aging

Cited by 16 publications

References 150 publications

The Regulation of Bone Metabolism by the Liver

The Regulation of Bone Metabolism by the Liver

Immunoregulatory Roles of Osteopontin in Diseases

The role of immunosuppressive myofibroblasts in the aging process and age-related diseases

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