Dietary supplementation of vitamin B1 prevents the pathogenesis of osteoarthritis.

As the primary cause for chronic pain and disability in elderly individuals, osteoarthritis (OA) is one of the fastest-growing diseases due to the aging world population. To date, the impact of microenvironmental changes on the pathogenesis of OA remains poorly understood, greatly hindering the development of effective therapeutic approaches against OA. In this study, we profiled the differential metabolites in the synovial fluid from OA patients and identified the downregulation of vitamin B1 (VB1) as a metabolic feature in the OA microenvironment. In a murine destabilization of medial meniscus-induced OA model, supplementation of VB1 significantly mitigated the symptoms of OA. Cytokine array analysis revealed that VB1 treatment remarkably reduced the production of a pro-OA factor-C-C Motif Chemokine Ligand 2 (CCL2), in macrophages. Further evidence demonstrated that exogenous CCL2 counteracted the anti-OA function of VB1. Hence, our study unveils a unique biological function of VB1 and provides promising clues for the diet-based treatment of OA.

Biological functions and biomedical applications of extracellular vesicles derived from blood cells.

There is a growing interest in using extracellular vesicles (EVs) for therapeutic applications. EVs are composed of cytoplasmic proteins and nucleic acids and an external lipid bilayer containing transmembrane proteins on their surfaces. EVs can alter the state of the target cells by interacting with the receptor ligand of the target cell or by being internalised by the target cell. Blood cells are the primary source of EVs, and 1 µL of plasma contains approximately 1.5 × 107 EVs. Owing to their easy acquisition and the avoidance of cell amplification in vitro, using blood cells as a source of therapeutic EVs has promising clinical application prospects. This review summarises the characteristics and biological functions of EVs derived from different blood cell types (platelets, erythrocytes, and leukocytes) and analyses the prospects and challenges of using them for clinical therapeutic applications. In summary, blood cell-derived EVs can regulate different cell types such as immune cells (macrophages, T cells, and dendritic cells), stem cells, and somatic cells, and play a role in intercellular communication, immune regulation, and cell proliferation. Overall, blood cell-derived EVs have the potential for use in vascular diseases, inflammatory diseases, degenerative diseases, and injuries. To promote the clinical translation of blood cell-derived EVs, researchers need to perform further studies on EVs in terms of scalable and reproducible isolation technology, quality control, safety, stability and storage, regulatory issues, cost-effectiveness, and long-term efficacy.

l-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy.

Background: Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. l-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that l-arginine-derived compounds can play a regulatory role in bone homeostasis. Purpose: To investigate the specific effect of l-arginine on bone homeostasis. Methods: Mildly aged and ovariectomized mouse models were used to study the effects of l-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of l-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers. Results: We found that l-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. l-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that l-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, l-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model. Conclusion: l-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy. The Translational Potential of this Article: L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.

Targeting initial tumour-osteoclast spatiotemporal interaction to prevent bone metastasis.

Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast 'tumasteoclast'-a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling-killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals. This can inhibit the formation of migrasomes for decoupling and disrupt cell membrane for killing, thereby achieving early prevention of bone metastasis. This study provides a research model for exploring tumour cell behaviour in detail and a proof-of-concept for behaviour-targeting strategy.

Multifunctional nanomaterials via cell cuproptosis and oxidative stress for treating osteosarcoma and OS-induced bone destruction.

Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.

The transformation of multifunctional bio-patch to hydrogel on skin wounds for efficient scarless wound healing.

Hydrogels have been widely used in various biomedical applications, including skin regeneration and tissue repair. However, the capability of certain hydrogels to absorb exudate or blood from surrounding wounds, coupled with the challenge in their long-term storage to prevent bacterial growth, can pose limitations to their efficacy in biological applications. To address these challenges, the development of a multifunctional aloin-arginine-alginate (short for 3A) bio-patch capable of transforming into a hydrogel upon absorbing exudate or blood from neighboring wounds for cutaneous regeneration is proposed. The 3A bio-patch exhibits outstanding features, including an excellent porous structure, swelling properties, and biodegradability. These characteristics allow for the rapid absorption of wound exudates and subsequent transformation into a hydrogel that is suitable for treating skin wounds. Furthermore, the 3A bio-patch exhibits remarkable antibacterial and anti-inflammatory properties, leading to accelerated wound healing and scarless repair in vivo. This study presents a novel approach to the development of cutaneous wound dressing materials.

[Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion].

OBJECTIVE: To observe the cage subsidence after oblique lateral interbody fusion (OLIF) for lumbar spondylosis, summarize the characteristics of the cage subsidence, analyze causes, and propose preventive measures. METHODS: The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively analyzed. There were 43 males and 101 females, and the age ranged from 20 to 81 years old, with an average of (60.90±10.06) years old. Disease types:17 patients of lumbar intervertebral disc degenerative disease, 12 patients of giant lumbar disc herniation, 5 patients of discogenic low back pain, 33 patients of lumbar spinal stenosis, 26 patients of lumbar degenerative spondylolisthesis, 28 patients of lumbar spondylolisthesis with spondylolisthesis, 11 patients of adjacent vertebral disease after lumbar internal fixation, 7 patients of primary spondylitis in the inflammatory outcome stage, and 5 patients of lumbar degenerative scoliosis. Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis, and 87 patients of normal bone density. The number of fusion segments:124 patients of single-segment, 11 patients of two-segment, 8 patients of three-segment, four-segment 1 patient. There were 40 patients treated by stand-alone OLIF, and 104 patients by OLIF combined with posterior pedicle screw. Observed the occurrence of fusion cage settlement after operation, conducted monofactor analysis on possible risk factors, and observed the influence of fusion cage settlement on clinical results. RESULTS: All operations were successfully completed, the median operation time was 99 min, and the median intraoperative blood loss was 106 ml. Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients. The mean follow-up was (14.57±7.14) months from 6 to 30 months. During the follow-up, except for the patients of primary lumbar interstitial inflammation and some patients of lumbar spondylolisthesis with spondylolisthesis, the others all had different degrees of cage subsidence. Cage subsidence classification:119 patients were normal subsidence, and 25 patients were abnormal subsidence (23 patients were gradeⅠ, and 2 patients were gradeⅡ). There was no loosening or rupture of the pedicle screw system. The height of the intervertebral space recovered from the preoperative average (9.48±1.84) mm to the postoperative average (12.65±2.03) mm, and the average (10.51±1.81) mm at the last follow-up. There were statistical differences between postoperative and preoperative, and between the last follow-up and postoperative. The interbody fusion rate was 94.4%. The low back pain VAS decreased from the preoperative average (6.55±2.2 9) to the last follow-up (1.40±0.82), and there was statistically significant different. The leg pain VAS decreased from the preoperative average (4.72±1.49) to the final follow-up (0.60±0.03), and the difference was statistically significant (t=9.13, P<0.000 1). The ODI index recovered from the preoperative average (38.50±6.98)% to the latest follow-up (11.30±3.27)%, and there was statistically significant different. The complication rate was 31.3%(45/144), and the reoperation rate was 9.72%(14/144). Among them, 8 patients were reoperated due to fusion cage subsidence or displacement, accounting for 57.14%(8/14) of reoperation. The fusion cage subsidence in this group had obvious characteristics. The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group, Stand-alone OLIF group, 2 or more segments fusion group, and endplate injury group was higher than that in the normal bone mass group, OLIF combined with pedicle screw fixation group, single segment fusion group, and no endplate injury group, and the comparison had statistical differences. CONCLUSION: Cage subsidence is a common phenomenon after OLIF surgery. Preoperative osteopenia or osteoporosis, Stand-alone OLIF, 2 or more segments of fusion and intraoperative endplate injury may be important factors for postoperative fusion cage subsidence. Although there is no significant correlation between the degree of cage subsidence and clinical symptoms, there is a risk of cage migration, and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence, including reoperation.

Artificially reprogrammed stem cells deliver transcytosable nanocomplexes for improved spinal cord repair.

Stem cell transplantation holds great promise for restoring function after spinal cord injury (SCI), but its therapeutic efficacy heavily depends on the innate capabilities of the cells and the microenvironment at the lesion site. Herein, a potent cell therapeutic (NCs@SCs) is engineered by artificially reprogramming bone marrow mesenchymal stem cells (BMSCs) with oxidation-responsive transcytosable gene-delivery nanocomplexes (NCs), which endows cells with robust oxidative stress resistance and improved cytokine secretion. NCs@SCs can accumulate in the injured spinal cord after intravenous administration via chemotaxis and boost successive transcytosis to deliver NCs to neurons, augmenting ciliary neurotrophic factor (CNTF) production in both BMSCs and neurons in response to elevated ROS levels. Furthermore, NCs@SCs can actively sense and eliminate ROS and re-educate recruited M1-like macrophages into the anti-inflammatory M2 phenotype via a paracrine pathway, ultimately reshaping the inflammatory microenvironment. Synergistically, NCs@SCs exhibit durable survival and provide neuroprotection against secondary damage, enabling significant locomotor function recovery in SCI rats. Transcriptome analysis reveals that regulation of the ROS/MAPK signaling pathway is involved in SCI therapy by NCs@SCs. This study presents a nanomaterial-mediated cell-reprogramming approach for developing live cell therapeutics, showing significant potential in the treatment of SCI and other neuro-injury disorders.

An inducible long noncoding RNA, LncZFHX2, facilitates DNA repair to mediate osteoarthritis pathology.

Cartilage homeostasis is essential for chondrocytes to maintain proper phenotype and metabolism. Because adult articular cartilage is avascular, chondrocytes must survive in low oxygen conditions, and changing oxygen tension can significantly affect metabolism and proteoglycan synthesis in these cells. However, whether long noncoding RNA participate in cartilage homeostasis under hypoxia has not been reported yet. Here, we first identified LncZFHX2 as a lncRNA upregulated under physiological hypoxia in cartilage, specifically by HIF-1α. LncZFHX2 knockdown simultaneously accelerated cellular senescence, targeted multiple components of extracellular matrix metabolism, and increased DNA damage in chondrocytes. Through a series of in vitro and in vivo experiments, we identified that LncZFHX2 performed a novel function that regulated RIF1 expression through forming a transcription complex with KLF4 and promoting chondrocyte DNA repair. Moreover, chondrocyte-conditional knockout of LncZFHX2 accelerated injury-induced cartilage degeneration in vivo. In conclusion, we identified a hypoxia-activated DNA repair pathway that maintains matrix homeostasis in osteoarthritis cartilage.

CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications.

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes.

BACKGROUND: Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age-related osteoarthritis (OA). METHODS: The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model. RESULTS: Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR-152-3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin-1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL-10 signalling by antagonizing miR-152-3p-mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA. CONCLUSION: CircGNB1 regulated oxidative stress and OA progression via the miR-152-3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

A nano-conductive osteogenic hydrogel to locally promote calcium influx for electro-inspired bone defect regeneration.

Conductive nano-materials and electrical stimulation (ES) have been recognized as a synergetic therapy for ordinary excitable tissue repair. It is worth noting that hard tissues, such as bone tissue, possess bioelectrical properties as well. However, insufficient attention is paid to the synergetic therapy for bone defect regeneration via conductive biomaterials with ES. Here, a novel nano-conductive hydrogel comprising calcium phosphate-PEDOT:PSS-magnesium titanate-methacrylated alginate (CPM@MA) was synthesized for electro-inspired bone tissue regeneration. The nano-conductive CPM@MA hydrogel has demonstrated excellent electroactivity, biocompatibility, and osteoinductivity. Additionally, it has the potential to enhance cellular functionality by increasing endogenous transforming growth factor-beta1 (TGF-ß1) and activating TGF-ß/Smad2 signaling pathway. The synergetic therapy could facilitate intracellular calcium enrichment, resulting in a 5.8-fold increase in calcium concentration compared to the control group in the CPM@MA ES + group. The nano-conductive CPM@MA hydrogel with ES could significantly promote electro-inspired bone defect regeneration in vivo, uniquely allowing a full repair of rat femoral defect within 4 weeks histologically and mechanically. These results demonstrate that our synergistic strategy effectively promotes bone restoration, thereby offering potential advancements in the field of electro-inspired hard tissue regeneration using novel nano-materials with ES.

USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling.

Ubiquitination is a reversible post-translational modification implicated in cell differentiation, homeostasis, and organ development. Several deubiquitinases (DUBs) decrease protein ubiquitination through the hydrolysis of ubiquitin linkages. However, the role of DUBs in bone resorption and formation is still unclear. In this study, we identified DUB ubiquitin-specific protease 7 (USP7) as a negative regulator of osteoclast formation. USP7 combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its ubiquitination by impairing the Lys63-linked polyubiquitin chain. Such impairment leads to the suppression of receptor activator of NF-κB ligand (RANKL)-mediated nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation without affecting TRAF6 stability. USP7 also protects the stimulator of interferon genes (STING) against degradation, inducing interferon-ß (IFN-ß) expression in osteoclast formation, thereby inhibiting osteoclastogenesis cooperatively with the classical TRAF6 pathway. Furthermore, USP7 inhibition accelerates osteoclast differentiation and bone resorption both in vitro and in vivo. Contrarily, USP7 overexpression impairs osteoclast differentiation and bone resorption in vitro and in vivo. Additionally, in ovariectomy (OVX) mice, USP7 levels are lower than those in sham-operated mice, suggesting that USP7 plays a role in osteoporosis. Altogether, our data reveal the dual effect of USP7-mediated TRAF6 signal transduction and USP7-mediated protein degradation of STING in osteoclast formation.

[Analysis of the causes and clinical results of vertebral fracture during oblique lateral lumbar interbody fusion].

OBJECTIVE: To analyze the causes of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy, summarize the clinical results, and propose preventive measures. METHODS: Retrospective analysis was made on the data of 8 cases of lumbar spondylopathy and vertebral fracture treated by oblique lateral interbody fusion in three medical centers from October 2014 to December 2018. All were female, aged from 50 to 81 years with an average of 66.4 years. Disease types included 1 case of lumbar degenerative disease, 3 cases of lumbar spinal stenosis, 2 cases of lumbar degenerative spondylolisthesis and 2 cases of lumbar degenerative scoliosis. Preoperative dual energy X-ray bone mineral density test showed that 2 cases had T-value >-1 SD, 2 cases had T-value -1 to -2.5 SD, and 4 cases had T-value <-2.5 SD. Single segment fusion was in 5 cases, two segment fusion in 1 case and three segment fusion in 2 cases. Four cases were treated with OLIF Stand-alone and 4 cases were treated with OLIF combined with posterior pedicle screw fixation. Postoperative imaging examination showed vertebral fracture, and all of them were single vertebral fracture. There were 2 cases of right lower edge fracture of upper vertebral body at fusion segment, 6 cases of lower vertebral body fracture at fusion segment, and 6 cases with endplate injury and fusion cage partially embedded in vertebral body. Three cases of OLIF Stand-alone were treated with pedicle screw fixation via posterior intermuscular approach, while one case of OLIF Stand-alone and four cases of OLIF combined with posterior pedicle screw fixation were not treated specially. RESULTS: The 5 cases of initial operation and 3 cases of reoperation did not show wound skin necrosis or wound infection. The follow-up time was from 12 to 48 months with an average of 22.8 months. Visual analogue scale (VAS) of low back pain was preoperative decreased from 4 to 8 points (averagely 6.3 points) and postoperative 1 to 3 points (averagely 1.7 points) at the final follow-up. Oswestry disability index (ODI) was preoperative 39.7% to 52.4% (averagely 40.2%), and postoperative 7.9% to 11.2% (averagely 9.5%) at the final follow-up. During the follow-up, there was no loosening or fracture of the pedicle screw system, and no lateral displacement of the fusion cage;however, the fusion cage at the vertebral fracture segment had obvious subsidence. The intervertebral space height of vertebral fracture segment was preoperaive 6.7 to 9.2 mm (averagely 8.1 mm), and postoperative 10.5 to 12.8 mm (averagely 11.2 mm). The improvement rate after operation was 37.98% compared to preoperative. The intervertebral space height at final follow-up was 8.4 to 10.9 mm (averagely 9.3 mm), and the loss rate was 16.71% compared with that after operation. At the final follow-up, interbody fusion was achieved in all cases except for one that could not be identified. CONCLUSION: The incidence of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy is lower, and there are many reasons for fracture, including preoperative bone loss or osteoporosis, endplate injury, irregular shape of endplate, excessive selection of fusion cage, and osteophyte hyperplasia at the affected segment. As long as vertebral fracture is found in time and handled properly, the prognosis is well. However, it still needs to strengthen prevention.

[Comparison of clinical effect and muscle injury imaging between oblique lateral lumbar interbody fusion and transforaminal lumbar interbody fusion in the treatment of single-segment degenerative lumbar spinal stenosis].

OBJECTIVE: To compare the efficacy and muscle injury imaging between oblique lateral lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis. METHODS: The clinical data of 60 patients with single-segment degenerative lumbar spinal stenosis who underwent surgical treatment from January 2018 to October 2019 was retrospectively analyzed. The patients were divided into OLIF groups and TLIF group according to different surgical methods. The 30 patients in the OLIF group were treated with OLIF plus posterior intermuscular screw rod internal fixation. There were 13 males and 17 females, aged from 52 to 74 years old with an average of (62.6±8.3) years old. And 30 patients in the TLIF group were treated with TLIF via the left approach. There were 14 males and 16 females, aged from 50 to 81 years old with an average of (61.7±10.4) years old. General data including operative time, intraoperative blood loss, postoperative drainage volume, and complications were recorded for both groups. Radiologic data including disc height (DH), the left psoas major muscle, multifidus muscle, longissimus muscle area, T2-weighted image hyperintensity changes and interbody fusion or nonfusion were observed. Laboratory parameters including creatine kinase (CK) values on postoperative 1st and 5th days were analyzed. Visual analogue scale(VAS) and Oswestry disability index(ODI) were used to assess clinical efficacy. RESULTS: There was no significant difference in the operative time between two groups(P>0.05). The OLIF group had significantly less intraoperative blood loss and postoperative drainage volume compared to the TLIF group(P<0.01). The OLIF group also had DH better recovery compared to the TLIF group (P<0.05). There were no significant differences in left psoas major muscle area and the hyperintensity degree before and after the operation in the OLIF group (P>0.05). Postoperativly, the area of the left multifidus muscle and longissimus muscle, as well as the mean of the left multifidus muscle and longissimus muscle in the OLIF group, were lower than those in the TLIF group (P<0.05) .On the 1st day and the 5th day after operation, CK level in the OLIF group was lower than that in the TLIF group(P<0.05). On the 3rd day after operation, the VAS of low back pain and leg pain in the OLIF group were lower than those in the TLIF group (P<0.05). There were no significant differences in the ODI of postoperative 12 months, low back and leg pain VAS at 3, 6, 12 months between the two groups(P>0.05). In the OLIF group, 1 case of left lower extremity skin temperature increased after the operation, and the sympathetic chain was considered to be injured during the operation, and 2 cases of left thigh anterior numbness occurred, which was considered to be related to psoas major muscle stretch, resulting in a complication rate of 10% (3/30). In the TLIF group, one patient had limited ankle dorsiflexion, which was related to nerve root traction, two patients had cerebrospinal fluid leakage, and the dural sac was torn during the operation, and one patient had incision fat liquefaction, which was related to paraspinal muscle dissection injury, resulting in a complication rate of 13% (4/30). All patients achieved interbody fusion without cage collapse during the 6- month follow-up. CONCLUSION: Both OLIF and TLIF are effective in the treatment of single-segment degenerative lumbar spinal stenosis. However, OLIF surgery has obviously advantages, including less intraoperative blood loss, less postoperative pain, and good recovery of intervertebral space height. From the changes in laboratory indexes of CK and the comparison of the left psoas major muscle, multifidus muscle, longissimus muscle area, and high signal intensity of T2 image on imaging, it can be seen that the degree of muscle damage and interference of OLIF surgery is lower than that of TLIF.

Synergistic Effect of Magneto-Mechanical Bioengineered Stem Cells and Magnetic Field to Alleviate Osteoporosis.

Therapeutic bioengineering based on stem cell therapy holds great promise in biomedical applications. However, the application of this treatment is limited in orthopedics because of their poor survival, weak localization, and low cell retention. In this work, magneto-mechanical bioengineered cells consisting of magnetic silica nanoparticles (MSNPs) and mesenchymal stem cells (MSCs) are prepared to alleviate osteoporosis. The magneto-mechanical bioengineered MSCs with spatial localization, cell retention, and directional tracking capabilities could be mediated by a guided magnetic field (MF) in vitro and in vivo. Furthermore, high uptake rates of the MSNPs ensure the efficient construction of magnetically controlled MSCs within 2 h. In conjunction with external MF, the magneto-mechanical bioengineered MSCs have the potential for the activation of the YAP/ß-catenin signaling pathway, which could further promote osteogenesis, mineralization, and angiogenesis. The synergistic effects of MSNPs and guided MF could also decline bone resorption to rebalance bone metabolism in bone loss diseases. In vivo experiments confirm that the functional MSCs and guided MF could effectively alleviate postmenopausal osteoporosis, and the bone mass of the treated osteoporotic bones by using the bioengineered cells for 6 weeks is nearly identical to that of the healthy ones. Our results provide a new avenue for osteoporosis management and treatment, which contribute to the future advancement of magneto-mechanical bioengineering and treatment.

CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis.

Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.

Metabolite asymmetric dimethylarginine (ADMA) functions as a destabilization enhancer of SOX9 mediated by DDAH1 in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease with a series of metabolic changes accompanied by many altered enzymes. Here, we report that the down-regulated dimethylarginine dimethylaminohydrolase-1 (DDAH1) is accompanied by increased asymmetric dimethylarginine (ADMA) in degenerated chondrocytes and in OA samples. Global or chondrocyte-conditional knockout of ADMA hydrolase DDAH1 accelerated OA development in mice. ADMA induces the degeneration and senescence of chondrocytes and reduces the extracellular matrix deposition, thereby accelerating OA progression. ADMA simultaneously binds to SOX9 and its deubiquitinating enzyme USP7, blocking the deubiquitination effects of USP7 on SOX9 and therefore leads to SOX9 degradation. The ADMA level in synovial fluids of patients with OA is increased and has predictive value for OA diagnosis with good sensitivity and specificity. Therefore, activating DDAH1 to reduce ADMA level might be a potential therapeutic strategy for OA treatment.