mitochondrial-transfer-from-mouse-adipose-derived-mesenchymal-stem

Mitochondrial Transfer from Mouse Adipose-Derived Mesenchymal Stem Cells into Aged Mouse Oocytes

Due to the decline in the quantity and quality of oocytes related to age, the fertility of women over 35 years of age has declined sharply. The molecular ...

isolation-culture-three-kinds-umbilical-cord-mesenchymal-stem

Isolation and Culture of Three Kinds of Umbilical Cord Mesenchymal Stem Cells

Umbilical cord mesenchymal stem cells (UC-MSCs) are an important cell source for regenerative medicine. UC-MSCs can be isolated from the umbilical cord ...

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling plays important physiological roles in bone homeostasis by regulating multiple steps of osteoblast differentiation as well as its activity. However, its potential role in osteocytes has not been explored. In this study, we deleted Raptor, a specific and essential component of mTORC1, in osteocytes using Dmp1-Cre. Deletion of Raptor in osteocytes did not affect bone development and growth, but caused compartment-specific effects on bone mass. Osteocyte-specific deletion of Raptor had no obvious effect on cortical bone compartments, but led to increased trabecular bone mass. Mechanistically, Raptor deletion resulted in decreased bone resorption without altering bone formation activity. Thus, our study revealed an unexpected role of osteocyte-intrinsic mTORC1 signaling in limiting trabecular bone mass, suggesting that osteocyte-specific inhibition of mTORC1 may be used as a novel approach to treatment of osteoporosis.

Osteocyte-intrinsic mTORC1 signaling restrains trabecular bone accrual in mice.

 Wear particle-induced periprosthetic osteolysis (PPO) is a common long-term complication of total joint arthroplasty, and represents the major cause of aseptic loosening and subsequent implant failure. Previous studies have identified the central role of osteoclast-mediated bone resorption in the pathogenesis of PPO. Thus, therapeutic approaches of inhibiting osteoclast formation and activity are considered to be of great potential to prevent and treat this osteolytic disease. Hedgehog (Hh) signaling has been shown to play an important role in promoting osteoblast differentiation and bone formation. While Hh signaling is also implicated in regulating osteoclastogenesis, whether it can directly inhibit osteoclast differentiation and bone resorption remains controversial. Moreover, its potential therapeutic effects on PPO have never been assessed. In this study, we explored the cell-autonomous role of Hh signaling in regulating osteoclastogenesis and its therapeutic potential in preventing wear particle-induced osteolysis.  Hh signaling was activated in macrophages by genetically ablating  in these cells using  or by treating them with purmorphamine (PM), a pharmacological activator of Smoothened (Smo).  cell-autonomous effects of Hh pathway activation on RANKL-induced osteoclast differentiation and activity were evaluated by TRAP staining, phalloidin staining, qPCR analyses, and bone resorption assays.  evaluation of its therapeutic efficacy against PPO was performed in a murine calvarial model of titanium particle-induced osteolysis by μCT and histological analyses. Mechanistic details were explored in RANKL-treated macrophages through Western blot analyses.  We found that  deletion or PM treatment potently activated Hh signaling in macrophages, and strongly inhibited RANKL-induced TRAP osteoclast production, F-actin ring formation, osteoclast-specific gene expression, and osteoclast activity . Furthermore, we found that  deletion or PM administration significantly attenuated titanium particle-induced osteoclast formation and bone loss . Our mechanistic study revealed that activation of Hh signaling suppressed RANKL-induced activation of JNK pathway and downregulated protein levels of two key osteoclastic transcriptional factors, c-Fos and its downstream target NFATc1.  Both genetic and pharmacological activation of Hh signaling can cell-autonomously inhibit RANKL-induced osteoclast differentiation and activity  and protect against titanium particle-induced osteolysis . Mechanistically, Hh signaling hinders osteoclastogenesis partly through suppressing the JNK/c-Fos-NFATc1 cascade. Thus, Hh signaling may serve as a promising therapeutic target for the prevention and treatment of PPO and other osteolytic diseases.

Genetic and pharmacological activation of Hedgehog signaling inhibits osteoclastogenesis and attenuates titanium particle-induced osteolysis partly through suppressing the JNK/c-Fos-NFATc1 cascade.

Histology-based analyses are important tools to dissect cellular and molecular mechanisms of skeletal homeostasis, diseases, and regeneration. The success of these efforts is highly dependent on rapidly obtaining high-quality sections of mineralized skeletal tissues suitable for various analyses. However, the current techniques for preparing such sections are still far from satisfactory. This study aimed to develop a new approach for preparing high-quality undecalcified bone sections applicable to various histological analyses.

A modified tape transfer approach for rapidly preparing high-quality cryosections of undecalcified adult rodent bones.

To investigate the expression of formyl peptide receptor 2 (FPR2) in maternal blood, umbilical blood, and placenta of patients with gestational diabetes mellitus (GDM), and to analyze the changes of other pro-inflammatory cytokines in blood, including interleukin 33 (IL-33), IL-1β, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP), so as to reveal the pathogenesis of GDM.

Formyl peptide receptor-2 is upregulated in the blood and placenta of patients with gestational diabetes mellitus.

Oogenesis is a fundamental process of human reproduction, and mitochondria play crucial roles in oocyte competence. Mitochondrial ATP-dependent Lon protease 1 (LONP1) functions as a critical protein in maintaining mitochondrial and cellular homeostasis in somatic cells. However, the essential role of LONP1 in maintaining mammalian oogenesis is far from elucidated.

The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals.

Intensive fasting reduces thrombosis and improves innate immunity.

Intervertebral disc (IVD) degeneration (IDD) is one of the most widespread musculoskeletal diseases worldwide and remains an intractable clinical challenge. Currently, regenerative strategies based on biomaterials and biological factors to facilitate IVD repair have been widely explored. However, the harsh microenvironment, such as increased ROS and acidity, of the degenerative region impedes the efficiency of IVD repair. Here, an intelligent biodegradable nanoplatform using hollow manganese dioxide (H-MnO) was developed to modulate the degenerative microenvironment and release transforming growth factor beta-3 (TGF-β3), which may achieve good long-term therapeutic effects on needle puncture-induced IDD.

Controlled Release of TGF-β3 for Effective Local Endogenous Repair in IDD Using Rat Model.

The aim of this study was to describe a case of ovarian torsion necrosis due to delayed treatment of luteoma in a woman with IVF twin pregnancy who was misdiagnosed with acute appendicitis. We summarized the clinical manifestations and diagnosis of luteoma in a woman with IVF twin pregnancy and reviewed the relevant literature. We report the case of a 34-year-old Asian female who became pregnant through  fertilization (IVF) and had acute right underbelly pain at 26 weeks and 6 days of gestation, which was misdiagnosed as acute appendicitis. Written consent was obtained from the patient. After fasting for a short duration and receiving anti-inflammatory and intravenous fluid replacement treatment after admission, the woman experienced increased right lower abdominal pain without relief and decreased fetal movement. B-ultrasound and CT examination showed that luteoma torsion was possible, and we performed emergency surgical laparotomy. During the operation, it was found that the right ovary was enlarged, the fallopian tube was twisted 720 degrees, and there was no lesion in the appendix. The right necrotic ovary was removed, and pathological results showed a hemorrhagic corpus luteum in the right ovary. The patient's abdominal pain was relieved after the operation and the pregnancy was continued. This is a typical case of ovariectomy associated with a luteoma of pregnancy. Whether  fertilization and related procedures increase the risk of luteoma and whether they increase the risk of ovarian torsion necrosis in the case of luteoma formation are questions that need further study.

A case of excision of ovarian torsion necrosis due to luteoma in a female who conceived a twin pregnancy through in vitro fertilization misdiagnosed with acute appendicitis.

ArticleTotal : 2	Year
Publication title Cited by 5	2023
Publication title Cited by 6	2022

Article	Year
Osteocyte-intrinsic mTORC1 signaling restrains trabecular bone accrual in mice. Journal of cellular biochemistry\| PubMed ID: 30160781	2018
Genetic and pharmacological activation of Hedgehog signaling inhibits osteoclastogenesis and attenuates titanium particle-induced osteolysis partly through suppressing the JNK/c-Fos-NFATc1 c... Theranostics\| PubMed ID: 32550895	2020
A modified tape transfer approach for rapidly preparing high-quality cryosections of undecalcified adult rodent bones. Journal of orthopaedic translation\| PubMed ID: 33437628	2021
Formyl peptide receptor-2 is upregulated in the blood and placenta of patients with gestational diabetes mellitus. The journal of obstetrics and gynaecology research\| PubMed ID: 34235813	2021
The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals. EBioMedicine\| PubMed ID: 34974310	2022
Intensive fasting reduces thrombosis and improves innate immunity. Aging\| PubMed ID: 35431182	2022
Controlled Release of TGF-β3 for Effective Local Endogenous Repair in IDD Using Rat Model. International journal of nanomedicine\| PubMed ID: 35592099	2022
A case of excision of ovarian torsion necrosis due to luteoma in a female who conceived a twin pregnancy through in vitro fertilization misdiagnosed with acute appendicitis. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology\| PubMed ID: 36002954	2022

Yanjun Yang

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