BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells

Cho, Jae-Hwan; Lee, Jae Hyup; Lee, Kyung Mee; Lee, Choon-Ki; Shin, Dong‐Myung

doi:10.1007/s00223-021-00923-3

Cited by 10 publications

(4 citation statements)

References 50 publications

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“…BMP-2, an established pro-osteoblastogenic protein, can stimulate bone production in healthy, non-senescent BMSCs. However, in senescent cells recombinant BMP-2 upregulates pathways of inflammation, adipogenesis, and cell apoptosis ( 101 ). In mouse models, FOXP1, a regulator of the pro-adipogenic CEBPβ/δ complex in BMAT, has been shown to attenuate senescence through repressing p16 INK4A (encoded by CDKN2A ), a cell cycle repressor that functions by inducing a G1 phase arrest ( 102 ).…”

Section: Age-related Bmat Expansion Results In Decreased Immune Fidel...mentioning

confidence: 99%

The Implications of Bone Marrow Adipose Tissue on Inflammaging

et al. 2022

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Once considered an inert filler of the bone cavity, bone marrow adipose tissue (BMAT) is now regarded as a metabolically active organ that plays versatile roles in endocrine function, hematopoiesis, bone homeostasis and metabolism, and, potentially, energy conservation. While the regulation of BMAT is inadequately understood, it is recognized as a unique and dynamic fat depot that is distinct from peripheral fat. As we age, bone marrow adipocytes (BMAds) accumulate throughout the bone marrow (BM) milieu to influence the microenvironment. This process is conceivably signaled by the secretion of adipocyte-derived factors including pro-inflammatory cytokines and adipokines. Adipokines participate in the development of a chronic state of low-grade systemic inflammation (inflammaging), which trigger changes in the immune system that are characterized by declining fidelity and efficiency and cause an imbalance between pro-inflammatory and anti-inflammatory networks. In this review, we discuss the local effects of BMAT on bone homeostasis and the hematopoietic niche, age-related inflammatory changes associated with BMAT accrual, and the downstream effect on endocrine function, energy expenditure, and metabolism. Furthermore, we address therapeutic strategies to prevent BMAT accumulation and associated dysfunction during aging. In sum, BMAT is emerging as a critical player in aging and its explicit characterization still requires further research.

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Section: Age-related Bmat Expansion Results In Decreased Immune Fidel...mentioning

confidence: 99%

The Implications of Bone Marrow Adipose Tissue on Inflammaging

et al. 2022

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“…BMP-2 stimulation of senescent bone marrow mesenchymal stem cells (BMSCs) activated adipogenic and cell death pathways like NF-kB or p38-mitogen activated protein kinase (MAPK). In non-senescent bone marrow mesenchymal stem cells (BMSCs), BMP-2 activated bone-forming pathways such as SMAD, BMP, and TGFβ [83]. CK2 negatively regulates BMP-2-activated signaling [84].…”

Section: Bone Fracturementioning

confidence: 99%

Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach

Pandit,

DeGeorge,

Nohe

2024

Kinases and Phosphatases

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Protein kinase CK2 (CK2) influences one-fifth of the cellular phosphoproteome. It regulates almost all cellular pathways and is thus a critical switch between biological processes within a cell. Inhibition of CK2 reverses oncogene addiction of tumor and alters tumor microenvironment. The success of this strategy and its clinical translation opens new opportunities. Targeting CK2 in musculoskeletal disorders is promising. Clinical manifestations of these disorders include dysfunctional inflammation, dysregulated cell differentiation, and senescence. Processes regulated by CK2 include all of these. Its emerging role in senescence also indicates its function’s centrality in cellular metabolism. This review summarizes considerations for targeting CK2 in musculoskeletal disorders. We have discussed the implications of CK2-regulated processes in musculoskeletal disorders.

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“…BMP-2, a detected pro-osteoblastogenic protein, can stimulate bone formation in healthy, non-senescent BM-MSCs. However, in senescent cells, recombinant BMP-2 activates inflammatory, adipogenesis, and cell apoptosis pathways [75]. In mouse models, FOXP1-a regulator of the pro-adipogenic CEBPβ/δ complex in BMAs-has been shown to attenuate aging by downregulating p16 INK4A (encoded by CDKN2A), a cell-cycle repressor that induces G1 phase arrest [76].…”

Section: The Role Of Bone Marrow Adipocytes In Myelopoiesis In Obesitymentioning

confidence: 99%

Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms)

Todosenko,

Khaziakhmatova,

Malashchenko

et al. 2023

IJMS

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Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose regulation is mediated by their interactions with bone marrow adipocytes, the importance of a detailed study of the heterogeneous composition of monocytes at the molecular and systemic levels becomes clear. Research argues for monocytes as indicators of changes in the body’s metabolism and the possibility of developing therapeutic strategies to combat obesity and components of metabolic syndrome based on manipulations of the monocyte compound of the immune response. An in-depth study of the heterogeneity of bone-marrow-derived monocytes and adipocytes could provide answers to many questions about the pathogenesis of obesity and reveal their therapeutic potential.

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BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells

Cited by 10 publications

References 50 publications

The Implications of Bone Marrow Adipose Tissue on Inflammaging

The Implications of Bone Marrow Adipose Tissue on Inflammaging

Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach

Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms)

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