Cell-Free Fat Extract Prevents Tail Suspension–Induced Bone Loss by Inhibiting Osteocyte Apoptosis

Xu, Mingming; Du, Jingke; Cui, Junqi; Zhang, Shuangyan; Zhang, Shuhong; Deng, Mingwu; Zhang, Wenjie; Li, Hanjun; Yu, Zhifeng

doi:10.3389/fbioe.2022.818572

Cited by 12 publications

(17 citation statements)

References 34 publications

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“…6 ). Moreover, the effect of CEFFE on proliferation was reported in a study of skin repair, and an anti-apoptotic effect was reported in osteoporosis, which was consistent with our findings [ 18 , 35 ]. In addition to its effect on proliferation and apoptosis, CEFFE can also enhance the mitochondrial function of GCs.…”

Section: Discussionsupporting

confidence: 92%

Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

et al. 2022

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Background Premature ovarian insufficiency (POI) is a refractory disease that seriously affects the reproductive health of women and is increasing in incidence and prevalence globally. There is enormous demand to improve fertility in women with POI, while there is still lack of effective therapeutic methods in clinic. Cell-free fat extract (CEFFE) has been reported to contain thousands of active proteins which possess the ability to promote tissue repair in other diseases. In our study, we aimed to observe the efficacy and biosecurity of CEFFE on the repair of ovarian function and fertility of mice with POI and further explore the underlying mechanism. Methods In vivo, POI mice model, established by cyclophosphamide (CTX, 120 mg/kg) and busulfan (BUS, 12 mg/kg), was treated with CEFFE via the tail vein every two days for 2 weeks. Then, the weight of ovaries, estrous cycle and follicle count by H&E staining were measured. The content of AMH, E2 and FSH in serum was measured by Enzyme-linked immunosorbent assay. Fertility was evaluated by the number of oocytes retrieved, the development of embryos in vitro and the litter size. Biosecurity of parent mice and their pups were examined by body mass and visceral index. The proliferation and apoptosis of cells in ovaries were examined by immunohistochemistry and transmission electron microscopy. Furthermore, the mRNA-Seq of mouse ovarian granulosa cells was performed to explore underlying mechanism of CEFFE. In vitro, KGN cell line and human primary ovarian granulosa cells (hGCs) were treated with 250 μM CTX for 48 h with/without CEFFE. The proliferative ability of cells was detected by cell counting kit-8 assay (CCK-8) and EDU test; the apoptosis of cells was detected by TUNEL and flow cytometry. Results CEFFE recovered the content of AMH, E2 and FSH in serum, increased the number of follicles and the retrieved oocytes of POI mice (P < 0.05). CEFFE contributed to the development of embryos and improved the litter size of POI mice (P < 0.05). There was no side effect of CEFFE on parent mice and their pups. CEFFE contributed to the proliferation and inhibited the apoptosis of mouse granulosa cells in ovary, as well as in human ovarian granulosa cells (including KGN cell line and hGCs) (P < 0.05). Conclusions The treatment of CEFFE inhibited the apoptosis of granulosa cells and contributed to the recovery of ovarian function, as well as the fertility of mice with POI.

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Section: Discussionsupporting

confidence: 92%

Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

et al. 2022

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“…Additionally, recombinant irisin (R-irisin), cell-free fat extract, and injection of cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes (CMS) had protective effects on the bones [ 58 , 59 , 64 , 69 , 76 ].…”

Section: Resultsmentioning

confidence: 99%

“…Strontium ranelate is already used in OP treatment, where it showed a significant increase in BMD on PMP OP [ 126 , 127 ]. The injection of cell-free fat extract also has a positive effect on BL, because it alleviates the HLU-induced decrease in BV/TV, trabecular number, and cortical thickness [ 69 ]. Furthermore, the injection of CMS in mice exposed to HLU increased BMD, BV/TV, cortical thickness, and trabecular thickness and number, while reducing the number of OCs [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

Baran

Wehland

Schulz

et al. 2022

IJMS

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Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µg, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.

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“…Xu et al . demonstrated that CEFFE prevents osteocyte apoptosis in a tail-suspension mouse model by attenuating ROS production [13]. Yin et al .…”

Section: Discussionmentioning

confidence: 99%

“…The effect of CEFFE on the bone microarchitecture was evaluated in accordance with our previously published study [13]. Briefly, right tibias and vertebral bodies were harvested for high-resolution μCT analysis (μCT 80, Scanco, Zurich, Switzerland) at a resolution of 10 μm per voxel, 70 kV voltage, and 114 μA electric current.…”

Section: Methodsmentioning

confidence: 99%

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang¹,

Xu²,

Kan³

et al. 2022

Preprint

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Osteoclasts are cells which are primarily involved in bone remodeling and osteolytic bone diseases. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration, particularly in postmenopausal osteoporosis. However, given the limitations of current first-line osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell-free fat extract (CEFFE) is the liquid fraction obtained from human adipose tissues, which are enriched with a variety of cytokines and growth factors. This study aims to explore its pharmacologic effect on hyperactive osteoclast formation in vivo and in vitro. CEFFE exhibits excellent potentials to attenuate osteoclast-associated bone loss in an ovariectomy (OVX) mouse model and to inhibit RANKL-induced osteoclastogenesis in primary bone marrow-derived monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE-Cation) is identified as the main inhibitory component in osteoclast formation assay. Excessive reactive oxygen species (ROS) production is the main cause of osteoclast overactivation. According to LC-MS/MS analysis, the CEFFE-Cation fraction mainly consists of various antioxidant enzymes, extracellular matrix, and adipokines, which endow it with a superior antioxidant capacity. Calcium signaling contributes to osteoclast maturation. In addition to scavenging ROS, CEFFE-Cation is also capable of mitigating calcium oscillaion, calcineurin activation, and subsequent NFATc1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next-generation personalized antiresorptive agent for osteolytic bone disease treatment.

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Cell-Free Fat Extract Prevents Tail Suspension–Induced Bone Loss by Inhibiting Osteocyte Apoptosis

Cited by 12 publications

References 34 publications

Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

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