The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Da, Wacili; Lin, Tao; Zhu, Yuyan

doi:10.3389/fendo.2021.675385

Cited by 82 publications

(72 citation statements)

References 174 publications

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“…During osteoclast differentiation, the expression of proteins participating in the cell cycle is reduced to save energy [ 20 ]. The cell cycle is the most significantly regulated process in both SNCs and MNCs.…”

Section: Resultsmentioning

confidence: 99%

“…However, if the SNCs are replaced in the new environment, they can develop into multinuclear osteoclasts. Mature osteoclasts exhibit reduced expression of cell cycle- and DNA repair and replication-related genes to save energy consumption, as compared with that in immature and precursor cells [ 20 ]. Cell death signaling mediated by apoptosis is induced in mature osteoclasts followed by the downregulation of ATP [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mature osteoclasts exhibit reduced expression of cell cycle- and DNA repair and replication-related genes to save energy consumption, as compared with that in immature and precursor cells [ 20 ]. Cell death signaling mediated by apoptosis is induced in mature osteoclasts followed by the downregulation of ATP [ 20 ]. An et al showed that metabolism-related processes, such as the TCA cycle, are increased in multinuclear osteoclasts based on a comparison among precursor cells, intermediate osteoclasts, and multinuclear osteoclasts derived from RAW 264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

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Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

View full text Add to dashboard Cite

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“…Using the Alamar Blue assay where oxidation-reduction reactions occur based on enzymatic activity, several considerations must be done [ 33 ]. In the case of PBMCs, mitochondrial enzymes are involved during the maturation of monocytes toward OCs/pre-OCs; indeed, OC differentiation from the original mononuclear progenitor cells requires high metabolic reprogramming to maintain biosynthetic substrates and energy supply [ 34 ]. In this light, the mitochondrial energy metabolism is subjected to variations and the conversion of the resorufin dye can change from 24 h to 7 days.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Collagen-Based Nanostructured Biomimetic Systems with a Co-Culture of Human Bone-Derived Cells

Borciani

Montalbano

Melo

et al. 2021

Cells

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Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and other factors, is considered a potential alternative to conventional treatments. Innovative scaffolds need to be tested in in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs), the two main players of bone remodeling, is required to mimic their crosstalk and molecular cooperation. To this aim, two composite materials were developed, based on type I collagen, and containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. The developed nanostructured systems underwent genipin chemical crosslinking and were then tested with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors, for 2–3 weeks. The favorable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of cells, encouraging a further investigation of the developed bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE.

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“…Similar to macrophages, monocytes also undergo metabolic changes like, increase in glucose uptake, oxidative phosphorylation etc. during differentiating into osteoclast (101). Different environmental cues drive different metabolic changes and as a result, monocyte responds differently.…”

Section: Monocytesmentioning

confidence: 99%

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

2021

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Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.

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The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Cited by 82 publications

References 174 publications

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Assessment of Collagen-Based Nanostructured Biomimetic Systems with a Co-Culture of Human Bone-Derived Cells

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

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