PM2.5 exposure inhibits osteoblast differentiation by increasing the ubiquitination and degradation of Smad4.

Increasing epidemiological evidence has shown that PM2.5 exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM2.5 exposure enhanced the differentiation and function of osteoclasts by indirectly causing chronic inflammation, while the mechanism in osteoblasts remains unclear. In our study, toxic effects were evaluated by direct exposure of 20-80µg/ml PM2.5 to MC3T3-E1 cells and BMSCs. The results showed that PM2.5 exposure did not affect cell viability via proliferation and apoptosis, but significantly inhibited osteoblast differentiation in a dose-dependent manner. Osteogenic transcription factors Runx2 and Sp7 and other biomarkers Alp and Ocn decreased after PM2.5 exposure. RNA-seq revealed TGF-ß signaling was involved in PM2.5 exposure inhibited osteoblast differentiation, which led to P-Smad1/5 and P-Smad2 reduction in the nucleus by increasing the ubiquitination and degradation of Smad4. At last, the inflammation response increased in MC3T3-E1 cells with PM2.5 exposure. Moreover, the mRNA levels of Mmp9 increased in bone marrow-derived macrophage cells treated with the conditional medium collected from MC3T3-E1 cells exposed to PM2.5. Overall, these results indicated that PM2.5 exposure inhibits osteoblast differentiation and concurrently increases the maturation of osteoclasts. Our study provides in-depth mechanistic insights into the direct impact of PM2.5 exposure on osteoblast, which would indicate the unrecognized role of PM2.5 on osteoporosis.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Physiological functions of podosomes: From structure and function to therapy implications in osteoclast biology of bone resorption.

With increasing age, bone tissue undergoes significant alterations in composition, architecture, and metabolic functions, probably causing senile osteoporosis. Osteoporosis possess the vast majority of bone disease and associates with a reduction in bone mass and increased fracture risk. Bone loss is on account of the disorder in osteoblast-induced bone formation and osteoclast-induced bone resorption. As a unique bone resorptive cell type, mature bone-resorbing osteoclasts exhibit dynamic actin-based cytoskeletal structures called podosomes that participate in cell-matrix adhesions specialized in the degradation of mineralized bone matrix. Podosomes share many of the same molecular constitutions as focal adhesions, but they have a unique structural organization, with a central core abundant in F-actin and encircled by scaffolding proteins, kinases and integrins. Here, we conclude recent advancements in our knowledge of the architecture and the functions of podosomes. We also discuss the regulatory pathways in osteoclast podosomes, providing a reference for future research on the podosomes of osteoclasts and considering podosomes as a therapeutic target for inhibiting bone resorption.

Favorable revision-free survivorship of cemented arthroplasty following failed proximal femoral nail antirotation: a case series with a median follow-up of 10 years.

BACKGROUND: Given the ever-increasing rate of failure related to proximal femoral nail antirotation (PFNA), it is expected that an increasing number of PFNA individuals will undergo conversion to total hip arthroplasty (THA). The long-term survivorship of conversion of the initial PFNA to cemented THA is still debated. The aim of this retrospective study was to assess the long-term revision-free survivorship of cemented THAs after initial failures of PFNA in geriatric individuals. METHODS: Consecutive geriatric individuals who underwent secondary cemented THA after initial PFNA fixation from July 2005 to July 2018, were retrospectively identified from three medical centres. The primary outcome was revision-free survivorship estimated using the Kaplan-Meier method and Cox proportional hazards regression with revision for any reason as the endpoint; secondary outcomes were functional outcomes and key THA-related complications. Follow-ups occurred at 3 months, 6 months, 12 months and then every 12 months after conversion. RESULTS: In total, 186 consecutive patients (186 hips) were available for study inclusion. The median follow-up was 120.7 months (60-180 months) in the cohort. Kaplan-Meier survivorship with revision for any reason as the end point showed that the 10-year revision-free survival rate was 0.852 (95% confidence interval [CI], 0.771-0.890). Good functional outcomes were seen, and the HHS decreased markedly over the 24th month to the final follow-up interval from 92.2 to 75.1 (each p < 0.05). The overall rate of key THA-related complications was 16.1% (30/186). CONCLUSION: Cemented THA executed following initial PFNA failure may yield satisfactory revision-free survival and, at least for the initial 10 years after conversion, good functional outcomes and a 16.1% complication rate of key THA-related complications, which supports the trend towards increased use of cemented THA.

Novel prospects for scarless wound healing: The roles of myofibroblasts and adipocytes.

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

Dual-Action Icariin-Containing Thermosensitive Hydrogel for Wound Macrophage Polarization and Hair-Follicle Neogenesis.

Bone morphogenetic protein (BMP) pathway is essential for M2 macrophage polarization and hair-follicle neogenesis. Icariin, a flavonoid derived from Epimedium, is a mediator of the BMP pathway. Here, we develop a hydrogel formulation functionalized with icariin for regulation of macrophage polarization to accelerate wound healing and hair-follicle neogenesis. Compared to skin defects without icariin treatment, those treated with icariin+PEG hydrogel healed faster and had new hair follicles. Results in vivo showed that icariin+PEG hydrogel induced a higher level of M2 phenotypic transformation of macrophages. Moreover, icariin+PEG hydrogel significantly accelerated wound-repair process by reducing the invasion of inflammation, excessive deposition of collagen, immoderate activation of myofibroblasts, and increasing the regeneration of hair follicles. Furthermore, studies in vitro demonstrated that the icariin+PEG hydrogel induced macrophages to polarize to the M2 phenotype and dermal papilla cell to hair follicles. Finally, molecular analysis demonstrated that the icariin+PEG hydrogel increased the expression of BMP4 and Smad1/5 phosphorylation in skin wounds. These results demonstrate the therapeutic potential of icariin-containing thermosensitive hydrogels for inducing M2 macrophage polarization to accelerate wound healing and promote hair-follicle neogenesis by regulating the BMP pathway.

The uPA System Differentially Alters Fibroblast Fate and Profibrotic Ability in Skin Fibrosis.

Skin fibrosis is a common pathological feature of various diseases, and few treatment strategies are available because of the molecular pathogenesis is poorly understood. The urokinase-type plasminogen activator (uPA) system is the major serine protease system, and its components uPA, urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) are widely upregulated in fibrotic diseases, including hypertrophic scars, keloids, and scleroderma. Here, we found that the successful binding of uPA and uPAR activates the downstream peroxisome proliferator-activated receptor (PPAR) signalling pathway to reduce the proliferation, migration, and contraction of disease-derived fibroblasts, contributing to the alleviation of skin fibrosis. However, increased or robust upregulation of the inhibitor PAI-1 inhibits these effects, suggesting of the involvement of PAI-1 in skin fibrosis. Subsequent in vivo studies showed that uPAR inhibitors increased skin fibrosis in mouse models, while uPA agonists and PAI-1 inhibitors reversed these effects. Our findings demonstrate a novel role for the uPA system and highlights its relationships with skin fibrosis, thereby suggesting new therapeutic approaches targeting the uPA system.

Suppression of bone remodeling associated with long-term bisphosphonate treatment is mediated by microRNA-30a-5p.

Oral bisphosphonates (BPs) are a first-line treatment for osteoporosis. It is becoming a hot topic to identify new indicators for the early prediction of therapeutic effects and adverse reactions during the long-term use of BPs. To determine whether microRNA (miRNA) expression is modulated by long-term BPs treatment, we performed miRNA expression profiling analysis in patients receiving long-term BP treatment for postmenopausal OP. To assess the effect of BPs on miRNA expression, we used an Affymetrix Genechip miRNA array to analyze serum samples obtained from postmenopausal OP patients on long-term BP treatment and healthy controls. MiRNAs affected by BPs and their predicted targets were examined. We also investigated the effects of miRNA on osteoblast differentiation in vitro and on ovariectomy-induced bone loss in vivo. We observed that the level of miR-30a-5p was significantly increased in patients receiving long-term BP treatment for postmenopausal OP. Furthermore, miR-30a-5p was negatively correlated with bone formation. Consistent with this, in vitro osteoblast activity and matrix mineralization were increased by an antagomir of miR-30a-5p and decreased by an agomir of miR-30a-5p. We also found that miR-30a-5p directly targeted RUNX1 to inhibit osteoblastic differentiation. Consistent with the in vitro results, miR-30a-5p antagomir administration promoted bone formation in ovariectomized mice. Our findings identified miR-30a-5p as a novel mediator of long-term BP treatment that regulates bone formation in postmenopausal OP patients.

Fibroblasts: Heterogeneous Cells With Potential in Regenerative Therapy for Scarless Wound Healing.

In recent years, research on wound healing has become increasingly in-depth, but therapeutic effects are still not satisfactory. Occasionally, pathological tissue repair occurs. Influencing factors have been proposed, but finding the turning point between normal and pathological tissue repair is difficult. Therefore, we focused our attention on the most basic level of tissue repair: fibroblasts. Fibroblasts were once considered terminally differentiated cells that represent a single cell type, and their heterogeneity was not studied until recently. We believe that subpopulations of fibroblasts play different roles in tissue repair, resulting in different repair results, such as the formation of normal scars in physiological tissue repair and fibrosis or ulcers in pathological tissue repair. It is also proposed that scarless healing can be achieved by regulating fibroblast subpopulations.

Conversion from a failed proximal femoral nail anti-rotation to a cemented or uncemented total hip arthroplasty device: a retrospective review of 198 hips with previous intertrochanteric femur fractures.

BACKGROUND: At present, it is unclear which device (uncemented or cemented total hip arthroplasty [UTA or CTA, respectively]) is more suitable for the conversion of a failed proximal femoral nail anti-rotation (PFNA). The aim of this review was to assess the outcomes of failed PFNAs converted to a UTA or CTA device in elderly individuals with intertrochanteric femoral fractures (IFFs). METHODS: Two hundred fifty-eight elderly individuals (258 hips) with IFFs who underwent a conversion to a UTA or CTA device following failed PFNAs during 2007-2017 were retrospectively identified from the China Southern Medical Centre (CSMC) database. The primary endpoint was the Harris Hip Score (HHS); secondary endpoint was the key orthopaedic complication rate. RESULTS: The median follow-up was 65 months (60-69 months). Significant distinctions were observed (87.26 ± 16.62 for UTA vs. 89.32 ± 16.08 for CTA, p = 0.021; 86.61 ± 12.24 for symptomatic UTA vs. 88.68 ± 13.30 for symptomatic CTA, p = 0.026). A significant difference in the overall key orthopaedic complication rate was detected (40.8% [40/98] vs. 19.0% [19/100], p = 0.001). Apparent distinctions were detected in terms of the rate of revision, loosening, and periprosthetic fracture (11.2% for UTA vs 3.0% for CTA, p = 0.025; 13.2% for UTA vs 5.0% for CTA, p = 0.043; 10.2% for UTA vs 3.0% for CTA, p = 0.041, respectively). CONCLUSION: For elderly individuals with IFFs who suffered a failed PFNA, CTA devices may have a noteworthy advantage in regard to the revision rate and the rate of key orthopaedic complications compared with UTA devices, and CTA revision should be performed as soon as possible, regardless of whether these individuals have symptoms.

Favourable clinical outcomes following cemented arthroplasty after metal-on-metal total hip replacement: a retrospective study with a mean follow-up of 10 years.

BACKGROUND: Given the unexpected high rate of failure following metal-on-metal total hip replacement (MoM-THR), it is expected that more MoM-THR patients will experience revision. The long-term outcomes regarding the primary MoM-THR revised to cemented THR (CTHR) remain controversial. The purpose of this retrospective review was to evaluate the long-term outcomes of patients who underwent conversion from MoM-THR to CTHR. METHODS: A total of 220 patients (220 hips) who underwent a conversion of primary MoM-THR to CTHR from March 2006 to October 2016 were retrospectively reviewed. The primary outcomes were the functional outcomes assessed using the Harris hip scores (HHS) and major radiographic outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every two years after revision. RESULTS: Mean follow-up was 10.1 years (5-13 years). Distinct improvements were detected in the mean HHS between the preoperative and last follow-up analysis (62.35[±8.49] vs. 84.70[±14.68], respectively, p < 0.001). The key orthopaedic complication rate was 18.2% (27/148). Seven (4.7%) cases experienced a CTHR failure at a mean of 3.4 (±1.2) years after revision MoM-THR, mostly attributed to recurrent dislocation. CONCLUSION: CTHR might yield an acceptable functional score and a low rate of the key orthopaedic complications.

Conversion to hemi-shoulder arthroplasty or reverse total shoulder arthroplasty after failed plate osteosynthesis of proximal humerus fractures: a retrospective study.

OBJECTIVE: To assess the clinical outcomes of hemi-shoulder arthroplasty (HSA) versus reverse total shoulder arthroplasty (RTSA) following failed plate osteosynthesis of proximal humerus fractures in elderly patients. METHODS: This retrospective study identified all patients that had a documented failed plate osteosynthesis of proximal humeral fractures treated with revision HSA or RTSA. Follow-up occurred at 1, 3, 6 and 12 months after surgery and every year thereafter. The primary outcomes were the American Shoulder and Elbow Surgeons (ASES) scores, Simple Shoulder Test (SST) scores, visual analogue scale (VAS) pain scores and the University of California, Los Angeles Shoulder Rating Scale (UCLA SRS) scores. The secondary outcome was the rate of major complications. RESULTS: A total of 126 patients (126 shoulders) were enrolled in the study. At the final follow-up, the RTSA group had significantly greater improvements in ASES, SST and UCLA SRS scores than the HSA group. The RTSA group had significantly larger decreases in the VAS pain score compared with the HSA group. The rate of major complications was significantly higher in the HSA group than in the RTSA group (44.4% versus 27.5%, respectively). CONCLUSION: RTSA provided superior functional outcomes compared with HSA, with a lower rate of major complications after a follow-up period of at least 5 years.

Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer.

OBJECTIVE: To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). METHODS: From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5-38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4-24.4) and 17.7 months (95% CI 11.3-19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15-0.46); median OS was 26.0 months (95% CI 23.4-28.7) and 22.7 months (95% CI 21.2-24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11-0.37). CONCLUSIONS: CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.

Long-term survival after cemented versus uncemented total hip arthroplasty for treatment of acute femoral neck fracture: a retrospective study with a mean 10-year follow-up.

OBJECTIVE: To compare the long-term survivorship and Harris hip scores (HHSs) between cemented total hip arthroplasty (CTHA) and uncemented total hip arthroplasty (UTHA) for treatment of acute femoral neck fractures (FNFs). METHODS: Data of 224 hips (CTHA, n = 112; UTHA, n = 112) that underwent primary surgery in our medical institution from 2005 to 2017 were retrospectively analysed. The primary endpoint was the risk of all-cause revision. The difference in the risk of all-cause revision between the two groups was assessed by Kaplan-Meier survival analysis with a log-rank test and Cox regression analysis. RESULTS: The mean postoperative follow-up was 10 years (range, 3-13 years). The Kaplan-Meier estimated 10-year implant survival rate was significantly higher in the CTHA than UTHA group (98.1% vs. 96.2%, respectively). The adjusted Cox regression analysis demonstrated a significantly lower risk of revision in the CTHA than UTHA group. At the final follow-up, the mean HHS was significantly higher in the CTHA than UTHA group (85.10 vs. 79.11, respectively). CONCLUSION: This retrospective analysis demonstrated that CTHA provided higher survival, lower revision risk, and higher functional outcome scores than UTHA. Further follow-up is necessary to verify whether these advantages of CTHA persist over time.

Uncemented versus cemented total hip arthroplasty for displaced femoral neck fractures in elderly patients with osteoporosis: A retrospective analysis.

OBJECTIVE: This study was performed assess the clinical outcomes of elderly patients with osteoporotic femoral neck fractures (FNFs) (AO/OTA: 31B/C) treated by initial uncemented total hip arthroplasty (UTA) or cemented total hip arthroplasty (CTA). METHODS: This study involved consecutive elderly patients with osteoporotic FNFs (AO/OTA: 31B/C) treated by initial UTA or CTA in our medical centre from 2010 to 2015. The primary outcomes were the Harris hip score (HHS) and the rates of revision, loosening, periprosthetic fracture, and dislocation. RESULTS: In total, 224 patients were included in the final analysis (UTA, n = 114; CTA, n = 110). The mean follow-up duration was 60 months (range, 32-68 months). The mean HHS was 75.34 ± 18.82 for UTA and 80.12 ± 17.83 for CTA. Significant dissimilarities were detected in the rates of revision, loosening, and periprosthetic fracture between UTA and CTA (14.0% vs. 5.5%, 20.2% vs. 10.0%, and 12.3% vs. 4.5%, respectively). A significant difference was also detected in the probability of revision between the two groups. CONCLUSION: Elderly patients with osteoporotic FNFs (AO/OTA: 31B/C) treated with CTA show greater improvements in functional outcomes and key orthopaedic complications than those treated with UTA.

Mid-term outcomes of uncemented or cemented arthroplasty revision following metal-on-metal total hip arthroplasty failure: a retrospective observational study.

OBJECTIVE: To retrospectively compare the mid-term outcomes of uncemented or cemented total hip arthroplasty (THA) revision for prior primary metal-on-metal (MoM) THA failure. METHODS: Data from 278 patients (278 hips) who underwent uncemented THA (UTHA) or cemented THA (CTHA) for prior primary MoM-THA failure from 2006 to 2016 were retrospectively analysed. Follow-up was performed 6 months, 1 year, 2 years, and then every 2 years after conversion. The mean follow-up time was 96 months (range, 64-128 months). The primary endpoint was the modified Harris hip score (HHS). The secondary endpoint was the major orthopaedic complication rate. RESULTS: The HHS showed significantly greater differences in the CTHA than UTHA group 12 months after conversion. From the 12th month after conversion to the final follow-up, CTHA yielded better functional outcomes than UTHA. There were significant differences between the UTHA and CTHA groups in the rates of re-revision (14.4% vs. 4.9%, respectively), aseptic loosening (17.3% vs. 6.8%, respectively), and periprosthetic fracture (11.5% vs. 3.9%, respectively). CONCLUSION: CTHA has more advantages than UTHA in terms of improving functional outcomes and decreasing the major orthopaedic complication rate.

Association of dyslipidaemia with Alzheimer's disease in a cohort of postmenopausal women.

OBJECTIVE: To evaluate the association between dyslipidaemia and Alzheimer's disease (AD) in a cohort of postmenopausal women. METHODS: This retrospective study analysed data from postmenopausal women with early AD (group AD) and a cohort of healthy age- and sex-matched control subjects (group NC) that were considered to be within standard limits according to a neuropsychological assessment between March 2010 and March 2019. The primary endpoints were body mass index and lipid-related laboratory parameters, including leptin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, adiponectin, triglycerides, apolipoprotein A1, apolipoprotein B and apolipoprotein E4, which were evaluated using multivariate binary logistic analysis. RESULTS: The study enrolled 200 postmenopausal women with early AD (mean ± SD age 69.34 ± 6.25 years) and 180 control subjects (mean ± SD age 67.48 ± 7.42 years). Lower HDL-C and higher LDL-C were risk factors for AD. A multivariate binary logistic regression model demonstrated that lower HDL-C and higher LDL-C were the only variables associated with the development of AD (odds ratio [OR] 21.14, 95% confidence interval [CI] 2.47, 4.13; OR 36.35, 95% CI 1.24, 3.38; respectively). CONCLUSION: Both low HDL-C and high LDL-C were associated with the occurrence of AD in a cohort of postmenopausal women.

Correlation between common postoperative complications of prolonged bed rest and quality of life in hospitalized elderly hip fracture patients.

BACKGROUND: Reduced postoperative mobility predisposes older patients with hip fractures to a variety of complications, including acute cerebral infarction, pressure injury, deep vein thrombosis of the lower limbs, and lung and urinary tract infections caused by prolonged bed rest. This study was designed to explore the relationship between common postoperative complications of prolonged bed rest and quality of life in hospitalized elderly hip fracture patients, in an attempt to inform the development of relevant interventions. METHODS: A total of 502 patients aged 65 years or above who underwent hip fracture surgery in our center were enrolled in this study. The patients' basic information and details of complications during their hospitalization was obtained from the case report form. The patients received telephone follow-up after discharge, and their quality of life (QoL) was measured by using the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). RESULTS: During hospitalization, 98 patients (19.52%) experienced at least 1 common complication including acute cerebral infarction (n=15, 2.99%), pressure injury (n=25, 4.98%), deep vein thrombosis of the lower limbs (n=14, 2.79%), pulmonary infections (n=84, 16.73%), and urinary tract infections (n=30, 5.98%). The proportion of patients who reported problems including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression was higher in those who experienced complications. CONCLUSIONS: Active prevention of common complications caused by prolonged bed rest can improve the QoL and reduce the disease burden for elderly patients with hip fractures.

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress-induced mineralization by regulating PPi metabolism.

This study aimed to investigate the role of apoptotic bodies (Abs) from the oxidative stressed endplate chondrocytes in regulating mineralization and potential mechanisms. Endplate chondrocytes were isolated from rats and treated with H2O2 to induce oxidative stress. The calcium deposition for matrix mineralization in the cells was examined by histological staining. The expression levels of calcification-related genes in individual groups of cells were determined by quantitative real time-PCR (qRT-PCR). Subsequently, extracellular vesicles (EVs) were purified and characterized. The effect of treatment with H2O2 and/or Abs on the mineralization, extracellular PPi metabolism and related gene expression were determined. Oxidative stress significantly increased the mineralization and promoted the generation of main Abs from endplate chondrocytes. Abs were effectively endocytosed by endplate chondrocytes and co-localized with collagen (COL)-II in the cytoplasm, which enhanced the mineralization, alkaline phosphatase (ALP), osteocalcin (OCN), Runt-related transcription factor 2 (RUNX2) and COL-I expression in endplate chondrocytes. Furthermore, treatment either H2O2 or Abs significantly decreased PPi, but increased Pi production and treatment with both further enhancing the changes in endplate chondrocytes. Similarly, treatment either H2O2 or Abs significantly decreased the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ankylosis protein (ANK) expression and ENPP1 promoter activity, but increased the tissue-nonspecific alkaline phosphatase (TNAP) expression and TNAP promoter activity in endplate chondrocytes. Oxidative stress promoted the generation of Abs, which might enhance the oxidative stress-mediated mineralization in endplate chondrocytes by regulating the PPi metabolism.