Muscle-derived extracellular vesicles improve disuse-induced osteoporosis by rebalancing bone formation and bone resorption

Huang, He; Ma, Shixing; Xing, Xiaotao; Su, Xiaoxia; Xu, Xun; Tang, Qi; Gao, Xin; Yang, Jian; Li, Maojiao; Liang, Cheng; Wu, Yutao; Liao, Li; Tian, Weidong

doi:10.1016/j.actbio.2022.12.019

Cited by 22 publications

(14 citation statements)

References 64 publications

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“…Although the concentration of these isolated EVs was low, their effect to decrease or increase osteoclast formation was strong (Table 2). At low intensity, exercise has many positive effects on bone remodeling and strengthens the bone through, for example, EVs released from skeletal muscle tissue or myoblasts [53][54][55] or EVs released by osteocytes. 36 In our study, we found a similar connection between bone-strengthening response by EV's released after low-intensity loading.…”

Section: Discussionmentioning

confidence: 99%

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow‐derived hematopoietic progenitor cells and change their osteoclast‐modulating effect

Bratengeier,

Johansson,

Liszka

et al. 2023

The FASEB Journal

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Low‐intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high‐intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa‐Β ligand‐induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g) obtained after low‐intensity loading and induced by exosomes (100 000× g) obtained after high‐intensity loading. These osteoclast‐modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT‐independent exosome biogenesis (high intensity), as well as by inhibition of dynamin‐dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast‐modulating effect.

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Section: Discussionmentioning

confidence: 99%

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow‐derived hematopoietic progenitor cells and change their osteoclast‐modulating effect

Bratengeier,

Johansson,

Liszka

et al. 2023

The FASEB Journal

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“…He et al confirmed that the high expression of Prrx2 in C2C12 cell-derived EVs directly combined with the MIR22HG promoter and promoted its transcription and expression, after which the sponge miR-128 enhanced the expression and nuclear translocation of YAP, thereby promoting osteogenic differentiation in BMSCs. 139 It has also been reported that myocyte-derived EVs stimulated by atrophic muscle, 136 inflammation, 140 or oxidative stress. 141 can induce osteoblast senescence and aggravate osteoporosis.…”

Section: The Potential Role Of Evs Derived From Different Sources In ...mentioning

confidence: 99%

“… 135 Studies have confirmed that EVs derived from healthy skeletal muscle cells can promote the osteogenic differentiation of BMSCs and inhibit the formation of monocytic osteoclasts. 136 – 138 However, there have been few reports on the mechanism by which myocyte-derived EVs regulate osteoporosis. He et al confirmed that the high expression of Prrx2 in C2C12 cell-derived EVs directly combined with the MIR22HG promoter and promoted its transcription and expression, after which the sponge miR-128 enhanced the expression and nuclear translocation of YAP, thereby promoting osteogenic differentiation in BMSCs.…”

Section: The Potential Role Of Evs Derived From Different Sources In ...mentioning

confidence: 99%

The role and applications of extracellular vesicles in osteoporosis

Fang,

Yang,

Wang

et al. 2024

Bone Res

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Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture, which increases patient susceptibility to fragile fractures. The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles (EVs), which play crucial roles in both pathological and physiological contexts. EVs derived from various sources exert distinct effects on osteoporosis. Specifically, EVs released by osteoblasts, endothelial cells, myocytes, and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins, miRNAs, and cytokines. Conversely, EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation. Furthermore, the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising. Here, we review the current understanding of the impact of EVs on bone homeostasis, including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis. Furthermore, we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs. Finally, we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

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“…The current conservative treatment for osteoporosis is mainly anti‐bone resorption and anabolic therapy. [ 6 ] The main clinical drugs include bisphosphonates, calcitonin, estrogen, selective estrogen receptor modulators (SERMs), denosumab, and other drugs that inhibit bone resorption, as well as BMP‐2 and its derivatives, parathyroid hormone (PTH) and its derivatives, abaloparatide and other active factors that promote bone remodeling. [ 7 ] Teriparatide, a derivative of the PTH, exhibits good anti‐OP biological activity but suffers from many disadvantages such as inadequate active site exposure, administration only by intermittent, systemic means, high cost, and tendency to induce hypercalcemia and osteosarcoma formation.…”

Section: Introductionmentioning

confidence: 99%

A Recombinant Parathyroid Hormone‐Related Peptide Locally Applied in Osteoporotic Bone Defect

Wang,

Hu,

Lan

et al. 2023

Advanced Science

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The local application of drug-loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self-assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone-related peptide-1 (PTHrP-1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti-OP bone repair material provides a theoretical basis for clinical translational applications.

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Muscle-derived extracellular vesicles improve disuse-induced osteoporosis by rebalancing bone formation and bone resorption

Cited by 22 publications

References 64 publications

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow‐derived hematopoietic progenitor cells and change their osteoclast‐modulating effect

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow‐derived hematopoietic progenitor cells and change their osteoclast‐modulating effect

The role and applications of extracellular vesicles in osteoporosis

A Recombinant Parathyroid Hormone‐Related Peptide Locally Applied in Osteoporotic Bone Defect

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