Degenerative Bone Disease Research Articles

3,3′-Diindolylmethane promotes bone formation – A assessment in MC3T3-E1 cells and zebrafish

Osteoporosis is a common degenerative bone disease in middle-aged and elderly people. The current drugs used to treat osteoporosis have many side effects and low patient compliance. Phytochemotherapy may be safer and more effective. 3,3′-diindolemethane (DIM) is the digestive product of indole-3-methanol in cruciferous vegetables in the stomach, which is a kind of anti-tumor and anti-oxidation phytochemical. However, the effects of DIM on osteoblasts and the mechanism by which DIM regulates bone formation are not fully understood. The aim of this study was to investigate the effects of DIM on the bone formation of mouse preosteoblasts MC3T3-E1 and zebrafish. DIM promotes proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro, and also plays a bone promoting role by increasing the interaction between BRCA1-Associated Protein 1(BAP1) and Inositol 1,4,5-Trisphosphate Receptor(IP3R), up-regulating the expression of BAP1 and IP3R and downstream storage operation calcium entry (SOCE) related protein Recombinant Stromal Interaction Molecule 1(STIM1). The effect of DIM on osteoporosis was confirmed in zebrafish osteoporosis model, and its molecular mechanism may be related to BAP1/IP3R/SOCE signaling pathway. These findings highlight the potential therapeutic value of DIM in the prevention and treatment of osteoporosis.

Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis.

Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, and chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, and necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to the pathogenesis of DBJDs, and targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti-inflammatory and antioxidant properties, have shown unique advantages in preventing DBJDs, potentially through modulating ferroptosis. This article provides an overview of the latest research on ferroptosis, with a focus on its role in the pathogenesis of DBJDs and the therapeutic potential of natural products targeting this cell death pathway, offering novel insights for the prevention and treatment of DBJDs.

Sulfated galactofucan from Sargassum fusiforme protects against postmenopausal osteoporosis by regulating bone remodeling

Osteoporosis is a degenerative bone disease highly prevalent in older women, causing high morbidity and mortality rates. Fourteen kinds of fucoidan were isolated from Sargassum fusiforme through acid (named as SFS), alkaline (SFJ) and water (SFW). SFW was passed through an anion exchange column to obtain SFW-0, SFW-0.5 and SFW-2. SFW-0.5 and SFW-2 were degraded to obtain different sulfate group contents SFW-x-M/S/O (x for 0.5 or 2). We further confirmed SFW-0.5-O was the most effective fraction of SFW. SFW-0.5-O may have alternating backbones of (Gal)n and (Fuc)n, and the main sulfation may be at C2/C3 of the Fuc/Gal residues. SFW-0.5-O inhibition of OC differentiation was associated with IRF-8 signaling; meanwhile, SFW-0.5-O promoted osteoblast differentiation and bone mineral nodule formation. SFW-0.5-O also effectively ameliorated osteoporosis symptom caused by estrogen deprivation in vivo. We uncovered that the fucoidan active fraction SFW-0.5-O demonstrated effective bone protection, may be exploited for osteoporosis therapy.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

Exploring the osteogenic effects of simiao wan through activation of the PI3K/AKT pathway in osteoblasts

Ethnopharmacological relevanceOsteoporosis (OP) is a degenerative bone disease commonly associated with reduced bone density and increased fracture risk. Aim of the studyThis study aimed to validate the therapeutic effects of Simiao wan (SMW) on OP and explore the underlying mechanism, particularly focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Materials and methodsThe chemical components of SMW were identified using UPLC-Q-TOF-MS/MS. The obtained compounds were then input into the TCMSP, TargetNet, and SwissTargetPrediction databases to predict potential targets. OP-related targets were collected from the GeneCards and DisGeNET databases, and intersecting targets were identified through a Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the intersecting targets using the Database for Annotation, Visualization and Integrated Discovery (DAVID). SMW extract was subsequently used to treat osteoblasts in vitro, and its toxicity on osteoblasts was assessed using Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Osteoblast differentiation and activity were further evaluated using alizarin red staining, alkaline phosphatase staining, and Western blot analyses to validate the activation of network pharmacological signaling pathways. ResultsA total of 121 potential targets were identified for SMW in the treatment of OP, with AKT1 as the primary target. The PI3K/AKT pathway emerged as a key signaling pathway potentially involved in SMW's therapeutic effects o OP. Toxicity assessments showed no significant toxicity of SMW on osteoblasts. Additionally, SMW promoted osteoblast proliferation, alkaline phosphatase activity, calcium nodule deposition, and the expression of osteogenic markers (osteocalcin (OCN), runt-related transcription factor 2 (RunX2), and collagen I), and activated the PI3K/AKT signaling pathway. The PI3K/AKT pathway inhibitor LY294002 partially reversed the SMW-induced mineral deposition and expression of OCN, RunX2, and collagen I. ConclusionSMW demonstrated effective multi-target and multi-pathway therapeutic potential in the treatment of OP, with a significant impact on the PI3K/AKT signaling pathway.

Photobiomodulation Dose-Response on Adipose-Derived Stem Cell Osteogenesis in 3D Cultures.

Osteoporosis and other degenerative bone diseases pose significant challenges to global healthcare systems due to their prevalence and impact on quality of life. Current treatments often alleviate symptoms without fully restoring damaged bone tissue, highlighting the need for innovative approaches like stem cell therapy. Adipose-derived mesenchymal stem cells (ADMSCs) are particularly promising due to their accessibility, abundant supply, and strong differentiation potential. However, ADMSCs tend to favor adipogenic pathways, necessitating the use of differentiation inducers (DIs), three-dimensional (3D) hydrogel environments, and photobiomodulation (PBM) to achieve targeted osteogenic differentiation. This study investigated the combined effects of osteogenic DIs, a fast-dextran hydrogel matrix, and PBM at specific wavelengths and fluences on the proliferation and differentiation of immortalized ADMSCs into osteoblasts. Near-infrared (NIR) and green (G) light, as well as their combination, were used with fluences of 3 J/cm2, 5 J/cm2, and 7 J/cm2. The results showed statistically significant increases in alkaline phosphatase levels, a marker of osteogenic differentiation, with G light at 7 J/cm2 demonstrating the most substantial impact on ADMSC differentiation. Calcium deposits, visualized by Alizarin red S staining, appeared as early as 24 h post-treatment in PBM groups, suggesting accelerated osteogenic differentiation. ATP luminescence assays indicated increased proliferation in all experimental groups, particularly with NIR and NIR-G light at 3 J/cm2 and 5 J/cm2. MTT viability and LDH membrane permeability assays confirmed enhanced cell viability and stable cell health, respectively. In conclusion, PBM significantly influences the differentiation and proliferation of hydrogel-embedded immortalized ADMSCs into osteoblast-like cells, with G light at 7 J/cm2 being particularly effective. These findings support the combined use of 3D hydrogel matrices and PBM as a promising approach in regenerative medicine, potentially leading to innovative treatments for degenerative bone diseases.

Precise Lubrication and Protection of Cartilage Damage by Targeting Hydrogel Microsphere.

Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear and ultimately irreversible damage. This situation is particularly challenging for early-stage OA, as current bio-lubricants lack precise targeting for small inflammatory lesions. In this work, an antibody-mediated targeting hydrogel microspheres (HMS) is developed to precisely lubricate the local injury site of cartilage and prevent the progression of early OA. Anti-Collagen type I (Anti-Col1) is an antibody that targets cartilage injury sites in early OA stages. It is anchored on a HMS matrix made of Gelatin methacrylate (GelMA) and poly (sulfobetaine methacrylate) (PSBMA) to create targeted HMS (T-G/S HMS). The T-G/S HMS's high hydrophilicity, along with the dynamic interaction between its surficial Anti-Col1 and the Col1 on cartilage injury site, ensures its precise and effective lubrication of early OA lesions. Consequently, injecting T-G/S HMS into rats with early OA significantly slows disease progression and reduces symptoms. In conclusion, the developed injectable targeted lubricating HMS and the precisely targeted lubrication strategy represent a promising, convenient technique for treating OA, particularly for slowing the early-stage OA progression.

A Study of the Cell Biological Mechanisms of Hormonal Osteonecrosis of the Femoral Head

Hormonal necrosis of the femoral head is a common degenerative bone disease whose pathogenesis involves multiple factors in which hormones play an important role. Past studies have shown that hormones can affect the metabolism and function of osteoblasts, but their specific cell biological mechanisms are not yet fully understood. However, there are still many issues that need to be further investigated in order to deeply explore the pathophysiological mechanisms of hormonal osteonecrosis of the femoral head and provide a more reliable scientific basis for clinical practice.

Deep learning-based pseudo-CT synthesis from zero echo time MR sequences of the pelvis

ObjectivesTo generate pseudo-CT (pCT) images of the pelvis from zero echo time (ZTE) MR sequences and compare them to conventional CT.MethodsNinety-one patients were prospectively scanned with CT and MRI including ZTE sequences of the pelvis. Eleven ZTE image volumes were excluded due to implants and severe B1 field inhomogeneity. Out of the 80 data sets, 60 were used to train and update a deep learning (DL) model for pCT image synthesis from ZTE sequences while the remaining 20 cases were selected as an evaluation cohort. CT and pCT images were assessed qualitatively and quantitatively by two readers.ResultsMean pCT ratings of qualitative parameters were good to perfect (2–3 on a 4-point scale). Overall intermodality agreement between CT and pCT was good (ICC = 0.88 (95% CI: 0.85–0.90); p < 0.001) with excellent interreader agreements for pCT (ICC = 0.91 (95% CI: 0.88–0.93); p < 0.001). Most geometrical measurements did not show any significant difference between CT and pCT measurements (p > 0.05) with the exception of transverse pelvic diameter measurements and lateral center-edge angle measurements (p = 0.001 and p = 0.002, respectively). Image quality and tissue differentiation in CT and pCT were similar without significant differences between CT and pCT CNRs (all p > 0.05).ConclusionsUsing a DL-based algorithm, it is possible to synthesize pCT images of the pelvis from ZTE sequences. The pCT images showed high bone depiction quality and accurate geometrical measurements compared to conventional CT.Critical relevance statementpCT images generated from MR sequences allow for high accuracy in evaluating bone without the need for radiation exposure. Radiological applications are broad and include assessment of inflammatory and degenerative bone disease or preoperative planning studies.Key PointspCT, based on DL-reconstructed ZTE MR images, may be comparable with true CT images.Overall, the intermodality agreement between CT and pCT was good with excellent interreader agreements for pCT.Geometrical measurements and tissue differentiation were similar in CT and pCT images.Graphical

“Three birds, one stone” strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis

Osteoporosis (OP), the most prevalent bone degenerative disease, has become a significant public health challenge globally. Current therapies primarily target inhibiting osteoclast activity or stimulating osteoblast activation, but their effectiveness remains suboptimal. This paper introduced a “three birds, one stone” therapeutic approach for osteoporosis, employing upconversion nanoparticles (UCNPs) to create a dual-gas storage nanoplatform (UZPA-CP) targeting bone tissues, capable of concurrently generating carbon monoxide (CO) and hydrogen sulfide (H2S). Through the precise modulation of 808 nm near-infrared (NIR) light, the platform could effectively control the release of CO and H2S in the OP microenvironment, and realize the effective combination of promoting osteogenesis, inhibiting osteoclast activity, and improving the immune microenvironment to achieve the therapeutic effect of OP. High-throughput sequencing results further confirmed the remarkable effectiveness of the nanoplatform in inhibiting apoptosis, modulating inflammatory response, inhibiting osteoclast differentiation and regulating multiple immune signaling pathways. The gas storage nanoplatform not only optimized the OP microenvironment with the assistance of NIR, but also restored the balance between osteoblasts and osteoclasts. This comprehensive therapeutic strategy focused on improving the bone microenvironment, promoting osteogenesis and inhibiting osteoclast activity provides an ideal new solution for the treatment of metabolic bone diseases.

Quantitative Analysis of 99mTc-MDP SPECT-CT Data in Diagnosing Bone Metastases in Breast Cancer Patients

Background: In patients with advanced breast cancer (BC), distant metastases happen mainly in the skeleton. This study aimed to investigate the role of 99mTc-MDP SPECT/CT in the differential diagnosis of malignant bone lesions from degenerative benign bone diseases in female BC patients. Methods and Results: The study included 39 female BC patients who underwent a baseline 99mTc-MDP SPECT/CT bone scans. After lesion detection, a quantitative radiotracer uptake analysis was conducted, and the standardized uptake value (SUVmax) was identified in each patient, and the data were then statistically analyzed. SUVmax values were significantly higher in BC patients with malignant metastasis than in patients with degenerative changes (33.04±15.3 vs. 13.25±5.46 g/mL, P&lt;0.05). The SUVmax cut-off value of 22.75 g/mL (25th percentile) obtained through box plot analysis can help to discriminate metastatic from degenerative lesions. The logistic regression analysis indicated that the SUVmax was a significant predictor of metastatic BL (P&lt;0.001, OR = 159.90, B=5.07). Conclusion: Our results suggested that quantitative analysis of the 99mTc-MDP SPECT-CT data can improve diagnostic accuracy in differentiating malignant metastatic bone lesions from degenerative bone lesions in high-risk BC patients.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Apoptotic Vesicles Derived from Dental Pulp Stem Cells Promote Bone Formation through the ERK1/2 Signaling Pathway.

Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.

Garcinol prevents oxidative stress-induced bone loss and dysfunction of BMSCs through NRF2-antioxidant signaling

There are multiple published data showing that excessive oxidative stress contributes to bone loss and even bone tissue damage, and it is also correlated with the pathophysiology of bone degenerative diseases, including osteoporosis (OP). Garcinol, a polyisoprenylated benzophenone derivative, has been recently established as an anti-oxidant agent. However, it remains elusive whether Garcinol protects bone marrow mesenchymal stem cells (BMSCs) and bone tissue from oxidative stress-induced damage. Here, we explored the potential effects of Garcinol supplementation in ameliorating oxidative stimulation-induced dysfunction of BMSCs and bone loss in osteoporotic mice. In this study, we verified that Garcinol exerted potent protective functions in the hydrogen peroxide (H2O2)-induced excessive oxidative stress and dysfunction of BMSCs. Besides, Garcinol was also identified to improve the reduced bone mass and abnormal lineage commitment of BMSCs in the condition of OP by suppressing the oxidative stimulation. Subsequent analysis revealed that nuclear factor erythroid 2-related factor 2 (NRF2) might be a key regulator in the sheltering effects of Garcinol on the H2O2-regulated oxidative stress, and the protective functions of Garcinol was mediated by NRF2-antioxidant signaling. Collectively, Garcinol prevented oxidative stress-related BMSC damage and bone loss through the NRF2-antioxidant signaling, which suggested the promising therapeutic values of Garcinol in the treatment of oxidative stress-related bone loss. Therefore, Garcinol might contribute to treating OP.

3D printing technology and its combination with nanotechnology in bone tissue engineering.

With the graying of the world's population, the morbidity of age-related chronic degenerative bone diseases, such as osteoporosis and osteoarthritis, is increasing yearly, leading to an increased risk of bone defects, while current treatment methods face many problems, such as shortage of grafts and an incomplete repair. Therefore, bone tissue engineering offers an alternative solution for regenerating and repairing bone tissues by constructing bioactive scaffolds with porous structures that provide mechanical support to damaged bone tissue while promoting angiogenesis and cell adhesion, proliferation, and activity. 3D printing technology has become the primary scaffold manufacturing method due to its ability to precisely control the internal pore structure and complex spatial shape of bone scaffolds. In contrast, the fast development of nanotechnology has provided more possibilities for the internal structure and biological function of scaffolds. This review focuses on the application of 3D printing technology in bone tissue engineering and nanotechnology in the field of bone tissue regeneration and repair, and explores the prospects for the integration of the two technologies.

Synthetic nanointerfacial bioengineering of Ti implants: on-demand regulation of implant-bone interactions for enhancing osseointegration.

Titanium and its alloys are the most commonly used biometals for developing orthopedic implants to treat various forms of bone fractures and defects, but their clinical performance is still challenged by the unfavorable mechanical and biological interactions at the implant-tissue interface, which substantially impede bone healing at the defects and reduce the quality of regenerated bones. Moreover, the impaired osteogenesis capacity of patients under certain pathological conditions such as diabetes and osteoporosis may further impair the osseointegration of Ti-based implants and increase the risk of treatment failure. To address these issues, various modification strategies have been developed to regulate the implant-bone interactions for improving bone growth and remodeling in situ. In this review, we provide a comprehensive analysis on the state-of-the-art synthetic nanointerfacial bioengineering strategies for designing Ti-based biofunctional orthopedic implants, with special emphasis on the contributions to (1) promotion of new bone formation and binding at the implant-bone interface, (2) bacterial elimination for preventing peri-implant infection and (3) overcoming osseointegration resistance induced by degenerative bone diseases. Furthermore, a perspective is included to discuss the challenges and potential opportunities for the interfacial engineering of Ti implants in a translational perspective. Overall, it is envisioned that the insights in this review may guide future research in the area of biometallic orthopedic implants for improving bone repair with enhanced efficacy and safety.

Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration.

Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) are the most common degenerative bone and joint diseases, posing a major threat to patients' physical and mental health due to the occurrence of chronic pain and disability. Within this context, the absence of efficacious therapies has led to a growing interest in regenerative medicine. In particular, as a method that can erase the memory of differentiation and re-endow cells with pluripotency, cell reprogramming technologies have ushered in a new era of personalized therapy, which not only show great potential for the treatment of degenerative osteoarthropathies but also promise to achieve tissue regenerative and repair. However, compared to other areas of research, reprogramming technologies to treat OA and IVDD are still in the preliminary stages and require further investigation. This paper briefly introduces the characteristics of cell reprogramming; summarizes the pathological mechanisms of reprogramming to improves energy metabolism, aging, inflammation, oxidative stress, and immune imbalance in OA and IVDD under the background of microenvironment and immunity; highlights the significant advantages of reprogramming-derived cells compared to embryonic stem cells and mesenchymal stem cells, based on these advances, providing important strategies for its development and clinical application in OA and IVDD.

The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism

IntroductionOsteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA. ObjectivesTo identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA. MethodsThe circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1. ResultsIt was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal’s.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14–3–3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity. ConclusionCircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future.

The composition of the blood microbiota and its relationship to osteoporosis-related clinical parameters

Osteoporosis, a systemic bone disease, is characterized by decreased bone mass, deterioration of skeletal structure, and increased bone susceptibility. Age, environment, hormone levels, nutrition, and immunity are all factors that influence bone mass. Currently, intestinal flora has been recently recognized as a key regulator of bone mass. The blood's microbiome role in bone health and in the pathogenesis of osteoporosis remains unknown. In this study, the abundance of various blood's microbial taxa in osteoporosis patients were analyzed. We investigated the associations between prominent bacterial taxa and other clinical indicators (i.e. biochemical, blood cell counts and CT scan). DNA was extracted from the whole blood samples of patients with degenerative bone diseases with or without osteoporosis (i.e. n = 8; ST and n = 12, T group) and healthy controls (n = 4, N group). The 16S rRNA gene sequencing technique was utilized to characterize the blood microbiome taxaThe Shannon–Winner and dilution curves revealed that all the characterized species in the sample and the sequencing data were reliable. The number of bacterial taxa in blood and annotated operational taxonomic units were positively correlated with neutrophils. This support that bacteria exist within or adhere to the neutrophil's membrane. The abundance of Yersinia ruckeri, Rhodanobacter_uncultured bacterium, Enterobacter spp., and Raoultella spp increased in the ST group as compared with the N group. Hence, indicate their potential role in the onset and progression of osteoporosis. These findings provide new insights into the association between blood microbiota and bone health. This study could open a new horizon in exploring the clinical application of blood microbiome to improve bone health.