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Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.

ABSTRACT: Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)-induced bone loss and age-related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCβ-NF-κB and MAPK1/3-STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell-derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders.

SUBMITTER: Xu X

PROVIDER: S-EPMC8892248 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.

Xu Xiaoli X Li Yixiang Y Shi Lingfeng L He Kaiyue K Sun Ying Y Ding Yan Y Meng Biying B Zhang Jiajia J Xiang Lin L Dong Jing J Liu Min M Zhang Junxia J Xiang Lingwei L Xiang Guangda G

EMBO reports 20220124 3

Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX ...[more]

PMID: 35068044

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Project description:Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.

Dataset Information

Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.

Publications

Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.

Similar Datasets

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