FoxO3 Regulates Mouse Bone Mesenchymal Stem Cell Fate and Bone-Fat Balance During Skeletal Aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation.

A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis.

Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models.

Exosomes derived from bone marrow mesenchymal stem cells pretreated with decellularized extracellular matrix enhance the alleviation of osteoarthritis through miR-3473b/phosphatase and tensin homolog axis.

Background: Osteoarthritis (OA) is a prevalent degenerative articular disease for which there is no effective treatment. Progress has been made in mesenchymal stem cell (MSC)-based therapy in OA, and the efficacy has been demonstrated to be a result of paracrine exosomes from MSCs. Decellularized extracellular matrix (dECM) provides an optimum microenvironment for the expansion of MSCs.

IL-1β contributes to the secretion of sclerostin by osteocytes and targeting sclerostin promotes spinal fusion at early stages.

Background: Despite extensive research, there is still a need for safe and effective agents to promote spinal fusion. Interleukin (IL)-1β is an important factor which influences the bone repair and remodelling. The purpose of our study was to determine the effect of IL-1β on sclerostin in osteocytes and to explore whether inhibiting the secretion of sclerostin from osteocytes can promote spinal fusion at early stages.

Ginger supplement significantly reduced length of hospital stay in individuals with COVID-19.

Background: Evidence from previous studies has suggested that ginger extract exhibits the potential as an alternative treatment for Coronavirus disease 2019 (COVID-19). Here, we want to investigate whether ginger supplement improves the clinical manifestation of hospitalized COVID-19 individuals.

Methods: A total of 227 hospitalized individuals with COVID-19 were randomized to either the control (n = 132) or intervention group (n = 95).

Biomechanical research of medial femoral circumflex vascularized bone-grafting in the treatment of early-to-mid osteonecrosis of the femoral head: a finite element analysis.

Purpose: Hip preservation therapy of early ONFH (Osteonecrosis of the femoral head) has emerged as one of the hot areas of research. We have optimized the procedure of traditional MFCVBG (medial femoral circumflex vascularized bone grafting) by using specialized surgical tools and used the finite element analysis to guide the implantation position of the bone flap during surgery and validate the biological mechanical stability of the modified MFCVBG.

Methods: This study was based on the data of a male patient with left hip (ARCO stage IIB, JIC type C) hormonal ONFH.

Stabilization of hypoxia-inducible factor-1α alleviates osteoarthritis via interacting with Per2 and resetting the circadian clock.

Objective: The study aimed to establish whether HIF1α entrains the core clock in chondrocytes and how the HIF1α affects the circadian rhythm.

Methods: We subjected primary chondrocytes to chronic circadian desynchrony (CCD) and subsequently treated with oxygen rhythm and dimethyloxalylglycine (DMOG). Circadian oscillations were analyzed with a real-time monitoring system of Per2 promoter activity and qPCR.

Iron overload-induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study.

Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether iron overload could lead to ferroptosis in osteoblasts and to explore whether ferroptosis of osteoblasts is involved in iron overload-induced osteoporosis in vitro and in vivo.

CLOCK regulates Drp1 mRNA stability and mitochondrial homeostasis by interacting with PUF60.

Circadian genes such as Clock, Bmal1, Cryptochrome1/2, and Period1/2/3 constitute the precise circadian system. Clock is a commonly used mouse model harboring a circadian clock gene mutation, which lacks the EXON-19-encoded 51 amino acids. Previous reports have shown that Clock mice have severe metabolic abnormalities.

Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity.

Background: Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine (L.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

Background: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH.

Development and validation of a prediction model for glucocorticoid-associated osteonecrosis of the femoral head by targeted sequencing.

Objective: To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults.

Methods: This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People's Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks.

Engeletin Protects Against TNF-α-Induced Apoptosis and Reactive Oxygen Species Generation in Chondrocytes and Alleviates Osteoarthritis in vivo.

Purpose: Osteoarthritis (OA) is a progressive disease characterized by pain and impaired joint functions. Engeletin is a natural compound with anti-inflammatory and antioxidant effects on other diseases, but the effect of engeletin on OA has not been evaluated. This study aimed to elucidate the protective effect of engeletin on cartilage and the underlying mechanisms.

Reciprocal effect of microRNA-224 on osteogenesis and adipogenesis in steroid-induced osteonecrosis of the femoral head.

The adverse effects of glucocorticoids (GCs) on bone marrow stromal stem cells (BMSCs) play an important role in steroid-induced osteonecrosis of the femoral head (ONFH). Our previous miRNA microarray analysis indicated that microRNA-224-5p (miR-224-5p) could be a potential regulator; however, the underlying mechanism remains unclear. In the present study, we demonstrated that miR-224-5p was upregulated in GC-treated BMSCs, and functional experiments revealed that miR-224-5p could suppress osteogenic but promote adipogenic differentiation of BMSCs.

Evaluation of efficacy and safety of percutaneous transforaminal endoscopic surgery (PTES) for surgical treatment of calcified lumbar disc herniation: a retrospective cohort study of 101 patients.

Background: Percutaneous transforaminal endoscopy has been widely used to treat lumbar disc herniation (LDH), but the steep learning curve and difficulties in removing the calcified disc hinders the application of conventional endoscopy in treating calcified lumbar disc herniation (CLDH). In 2017, we first reported Percutaneous Transforaminal Endoscopic Surgery (PTES) as an easy-to-learn posterolateral transforaminal endoscopic technique to decompress the nerve root for LDH. We used our PTES technique to remove the calcified LDH and the purpose of this study is to evaluate the safety and efficacy of this technique.

Matrix reverses immortalization-mediated stem cell fate determination.

Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential.

Pinocembrin alleviates glucocorticoid-induced apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway in osteocytes.

Glucocorticoids are widely used in clinical practice, but are associated with potentially severe side effects like glucocorticoid-induced osteoporosis (GIOP) and glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Glucocorticoid-induced osteocyte apoptosis plays critical roles in the pathological processes of both GIOP and GA-ONFH. Pinocembrin is a natural flavonoid that may exert protective effects on osteocytes.

Quantitative Characterization of Bone Viability of Femoral Head and Subchondral Bone by Using Single Photon Emission Computerized Tomography/Computerized Tomography (SPECT/CT).

BACKGROUND Vascularized fibular grafting (VFG) has been successfully employed for treating avascular necrosis of the femoral head (ANFH). In this study, we aimed to evaluate the bone viability of the femoral head and subchondral bone following VFG by using single photon emission computerized tomography and computerized tomography (SPECT/CT). MATERIAL AND METHODS Between March 2011 and June 2014, 14 ANFH patients (17 hips) treated with VFG at Zhongshan Hospital, Fudan University, were prospectively enrolled.

Degradation and osteogenic induction of a SrHPO-coated Mg-Nd-Zn-Zr alloy intramedullary nail in a rat femoral shaft fracture model.

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis.

Injectable double-crosslinked hydrogels with kartogenin-conjugated polyurethane nano-particles and transforming growth factor β3 for in-situ cartilage regeneration.

Articular cartilage has a limited ability for self-repair after injury. Implantation of scaffolds functionalized with bioactive molecules that could induce the migration and chondrogenesis of endogenous mesenchymal stem cells (MSCs) provides a convenient alternative for in-situ cartilage regeneration. In this study, we found the synergistic effects of kartogenin (KGN) and transforming growth factor β3 (TGF-β3) on chondrogenesis of MSCs in vitro, indicating that KGN and TGF-β3 are a good match for cartilage regeneration.

Impact of Fibronectin Knockout on Proliferation and Differentiation of Human Infrapatellar Fat Pad-Derived Stem Cells.

Fibronectin plays an essential role in tissue development and regeneration. However, the effects of fibronectin knockout (FN1-KO) on stem cells' proliferation and differentiation remain unknown. In this study, CRISPR/Cas9 generated FN1-KO in human infrapatellar fat pad-derived stem cells (IPFSCs) was evaluated for proliferation ability including cell cycle and surface markers as well as stemness gene expression and for differentiation capacity including chondrogenic and adipogenic differentiation.

Serum Biomarkers Related to Glucocorticoid-Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case-Control Study.

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH.