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Scientific Reports May 2024Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the...
Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the apoptosis of chondrocytes triggered by oxidative stress. Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported in the regulation of oxidative stress. However, there remains unclear mechanisms that through which PPARγ influences the pathogenesis of OA. The present study aims to delve into the role of PPARγ in chondrocytes apoptosis induced by oxidative stress in the context of OA. Primary human chondrocytes, both relatively normal and OA, were isolated and cultured for the following study. Various assessments were performed, including measurements of cell proliferation, viability and cytotoxicity. Additionally, we examined cell apoptosis, levels of reactive oxygen species (ROS), nitric oxide (NO), mitochondrial membrane potential (MMP) and cytochrome C release. We also evaluated the expression of related genes and proteins, such as collagen type II (Col2a1), aggrecan, inducible nitric oxide synthase (iNOS), caspase-9, caspase-3 and PPARγ. Compared with relatively normal cartilage, the expression of PPARγ in OA cartilage was down-regulated. The proliferation of OA chondrocytes decreased, accompanied by an increase in the apoptosis rate. Down-regulation of PPARγ expression in OA chondrocytes coincided with an up-regulation of iNOS expression, leading to increased secretion of NO, endogenous ROS production, and decrease of MMP levels. Furthermore, we observed the release of cytochrome C, elevated caspase-9 and caspase-3 activities, and reduction of the components of extracellular matrix (ECM) Col2a1 and aggrecan. Accordingly, utilization of GW1929 (PPARγ Agonists) or Z-DEVD-FMK (caspase-3 inhibitor) can protect chondrocytes from mitochondrial-related apoptosis and alleviate the progression of OA. During the progression of OA, excessive oxidative stress in chondrocytes leads to apoptosis and ECM degradation. Activation of PPARγ can postpone OA by down-regulating caspase-3-dependent mitochondrial apoptosis pathway.
Topics: Humans; Chondrocytes; PPAR gamma; Apoptosis; Caspase 3; Osteoarthritis; Mitochondria; Reactive Oxygen Species; Oxidative Stress; Membrane Potential, Mitochondrial; Cell Proliferation; Nitric Oxide; Cells, Cultured; Middle Aged; Aged; Female; Male
PubMed: 38755283
DOI: 10.1038/s41598-024-62116-w -
World Neurosurgery: X Jul 2024Robotic-assisted, endoscopic transforaminal lumbar interbody fusion (RE-TLIF) is a promising, minimally invasive surgical option for degenerative lumbar...
BACKGROUND
Robotic-assisted, endoscopic transforaminal lumbar interbody fusion (RE-TLIF) is a promising, minimally invasive surgical option for degenerative lumbar spondylosis/spondylolisthesis; however, outcomes data and efficacy are limited, especially in multilevel disease. Here, we present the first reported series of patients that underwent either single or multilevel RE-TLIF.
METHODS
A retrospective review was performed on 23 consecutive patients who underwent a single level or multilevel RE-TLIF by a single surgeon. Variables included demographics, perioperative results, pain scores, and functional outcome scores.
RESULTS
Eighteen patients (78.3 %) underwent single level RE-TLIF and 5 patients (21.7 %) underwent multilevel RE-TLIF. The median reduction of visual analog scale (VAS) for low back pain (LBP) of all subjects was 6 (IQR = 4.5, 6.5) with no significant difference between single level and multilevel RE-TLIF ( = 0.565). The median reduction of VAS for leg pain of all subjects 7 (IQR = 6, 8) with no significant difference between single level and multilevel RE-TLIF ( = 0.702). Median blood loss was 25 cc (IQR = 25, 25) and 50 cc (IQR = 25, 100) for single and multilevel RE-TLIF, respectively ( = 0.025), whereas median length of stay was 1 (IQR = 1, 1; mean = 1.0 ± 00.18) days and 1 (IQR = 1, 2; mean = 1.4 ± 00.54) days, respectively ( = 0.042). One major complication was observed requiring reoperation for demineralized bone matrix migration resulting in an L5 radiculopathy.
CONCLUSIONS
Single and multi-level RE-TLIF appears to be a safe and efficacious approach with comparable outcomes to open and other minimally invasive approaches. Additionally, we observed favorable accuracy in robot-assisted pedicle screw, endoscope, and interbody device placement.
PubMed: 38746041
DOI: 10.1016/j.wnsx.2024.100390 -
Frontiers in Immunology 2024Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs...
BACKGROUND
Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion.
OBJECTIVE
To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment.
METHODS
dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed.
RESULTS
Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin β1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs.
CONCLUSION
We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.
Topics: Animals; Mice; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Humans; Regeneration; Pulmonary Disease, Chronic Obstructive; Pulmonary Alveoli; Umbilical Cord; Cells, Cultured; Cell Differentiation; Cord Blood Stem Cell Transplantation; Mice, Inbred C57BL; Male
PubMed: 38745668
DOI: 10.3389/fimmu.2024.1384718 -
BMC Oral Health May 2024Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular...
BACKGROUND
Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA.
MATERIALS AND METHODS
To determine whether Dspp mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp, and Dspp homozygous (Dspp) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp mice over time, condyles of Dspp and WT mice were analyzed radiologically, histologically, and immunohistochemically.
RESULTS
Micro-CT and histomorphometric analyses revealed that Dspp and Dspp mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp mice which exhibited tooth loss, Dspp mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage.
CONCLUSIONS
Dspp mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
Topics: Animals; Osteoarthritis; Mice; X-Ray Microtomography; Sialoglycoproteins; Extracellular Matrix Proteins; Temporomandibular Joint Disorders; Phosphoproteins; Mandibular Condyle; Temporomandibular Joint
PubMed: 38745274
DOI: 10.1186/s12903-024-04320-8 -
Laboratory Animal Research May 2024Microgravity, a condition experienced in a spatial environment, poses unique challenges to the skeletal system, particularly in juvenile organisms. This study aimed to...
BACKGROUND
Microgravity, a condition experienced in a spatial environment, poses unique challenges to the skeletal system, particularly in juvenile organisms. This study aimed to investigate alterations in bone biomechanics of juvenile mice due to unloading - that simulates microgravity in the laboratory-and the effects of a bone-loading intervention. We compared bone compositional and mechanical properties between 21-six-week-old C57Bl/6 from a control group (wild type) and a group that underwent a tail-suspension unloading protocol to mimic microgravity (MG). The second group (MG) experienced additional in vivo loading protocol (MG + LDG) on the right hind leg, where dynamic compressive loading was applied to the right knee using a custom-built loading device.
RESULTS
Our results show that after two weeks, we successfully induced bone alterations by (i) decreasing the energy dissipated before fracture and (ii) decreasing the yield and maximum stress. In addition, we showed that Mineral to matrix component [ν1PO4/Amide I], Carbonate to Amide [CO3/Amide I], and Crystallinity [1/FWHM(ν1PO4)] are strongly linked in physiological bone but not in microgravity even after loading intervention. While Crystallinity is very sensitive to bone deformation (strain) alterations coming from simulated microgravity, we show that Carbonate to Amide [CO3/Amide I] - a common marker of turnover rate/remodeling activity-is a specific predictor of bone deformation for bone after simulated microgravity. Our results also invalidate the current parameters of the loading intervention to prevent bone alterations entirely in juvenile mice.
CONCLUSIONS
Our study successfully induced bone alterations in juvenile mice by using an unloading protocol to simulate microgravity, and we provided a new Raman Spectroscopy (RS) dataset of juvenile mice that contributes to the prediction of cortical bone mechanical properties, where the degree of interrelationship for RS data for physiological bone is improved compared to the most recent evidence.
PubMed: 38745255
DOI: 10.1186/s42826-024-00207-5 -
Bone Research May 2024Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying...
Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.
Topics: Animals; Osteoclasts; Lysosomes; Endosomes; Mice; Mice, Knockout; Bone Resorption; Protein Transport; Mice, Inbred C57BL; rab GTP-Binding Proteins; Cell Differentiation; Gene Deletion; Cathepsin K; Female; rab7 GTP-Binding Proteins
PubMed: 38744829
DOI: 10.1038/s41413-024-00326-8 -
European Journal of Dentistry May 2024The main principle in preventing periodontal disease is to improve oral hygiene. The bacteria that cause the onset of periodontal disease, one of which is the...
OBJECTIVE
The main principle in preventing periodontal disease is to improve oral hygiene. The bacteria that cause the onset of periodontal disease, one of which is the bacterium, causes inflammation. Persistent inflammation causes tissue damage and alveolar bone resorption by secreting proinflammatory cytokines, matrix metalloproteinase-9 (MMP-9), prostaglandin E2 (PGE-2), and anti-inflammatory cytokines. In this case, preventive treatment is needed, such as using toothpaste that contains anti-inflammatories so that the progression of the disease does not get worse. The traditional ingredient currently being developed is , which has anti-inflammatory properties. Therefore, this study analyzes the potential of toothpaste containing on the expression of tumor necrosis factor-α (TNF-α), MMP-9, and PGE-2 in the Wistar rat model induced by bacteria. This study aims to prove the potential of toothpaste to decrease the expression of PGE-2, TNF-α, and MMP-9 in the gingiva of rats induced by bacteria.
MATERIALS AND METHODS
Forty-five healthy male Wistar rats were used, consisting of the negative control group, which was only injected with bacteria ATCC3322. The positive control group was given enzyme toothpaste, and the treatment group was assigned 1 mg of paste using a microbrush for 30 seconds on the gingiva incisors mandibular with a circular motion, given two times a day for a week. Immunohistochemical to see the expression of TNF-α, PGE-2, and MMP-9. Parametric comparative analysis using a one-way analysis of variance test was performed to analyze differences between groups.
RESULTS AND DISCUSSION
toothpaste significantly reduced proinflammatory cytokines, as seen through the expression of TNF-α, PGE-2, and MMP-9 on days 3, 5, and 7 ( <0.05).
CONCLUSION
In the limit of studied animal model, this trial indicates that giving toothpaste with black seed extract () could inhibit inflammatory mediators, as seen from the decreased expression of MMP-9, TNF-α, and PGE-2 seen from the 3rd, 5th, and 7th days.
PubMed: 38744331
DOI: 10.1055/s-0043-1772700 -
Biology Open May 2024Bone is increasingly recognized as a target for diabetic complications. In order to evaluate the direct effects of high glucose on bone, we investigated the global...
Bone is increasingly recognized as a target for diabetic complications. In order to evaluate the direct effects of high glucose on bone, we investigated the global transcriptional changes induced by hyperglycemia in osteoblasts in vitro. Rat bone marrow-derived mesenchymal stromal cells were differentiated into osteoblasts for 10 days, and prior to analysis, they were exposed to hyperglycemia (25 mM) for the short-term (1 or 3 days) or long-term (10 days). Genes and pathways regulated by hyperglycemia were identified using mRNA sequencing and verified with qPCR. Genes upregulated by 1-day hyperglycemia were, for example, related to extracellular matrix organization, collagen synthesis and bone formation. This stimulatory effect was attenuated by 3 days. Long-term exposure impaired osteoblast viability, and downregulated, for example, extracellular matrix organization and lysosomal pathways, and increased intracellular oxidative stress. Interestingly, transcriptional changes by different exposure times were mostly unique and only 89 common genes responding to glucose were identified. In conclusion, short-term hyperglycemia had a stimulatory effect on osteoblasts and bone formation, whereas long-term hyperglycemia had a negative effect on intracellular redox balance, osteoblast viability and function.
Topics: Osteoblasts; Animals; Glucose; Rats; Gene Expression Regulation; Gene Expression Profiling; Hyperglycemia; Cell Differentiation; Mesenchymal Stem Cells; Transcriptome; Osteogenesis; Cell Survival; Transcription, Genetic; Cells, Cultured; Oxidative Stress
PubMed: 38742438
DOI: 10.1242/bio.060239 -
PloS One 2024We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac...
BACKGROUND
We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac magnetic resonance (CMR) and mortality in patients with ST-elevation myocardial infarction (STEMI).
METHODS
The concentrations of six ECM-related proteins (periostin, osteopontin, syndecan-1, syndecan-4, bone morphogenetic protein 7, and growth differentiation factor (GDF)-15) were measured in serum samples from patients on Day 1 and Month 4 after STEMI (n = 239). Ischemic injury was assessed by myocardial salvage index, microvascular obstruction, infarct size, and left ventricular function measured by CMR conducted during the initial admission (median 2 days after admission) and after 4 months. All-cause mortality was recorded after a median follow-up time of 70 months.
RESULTS
Levels of periostin increased from Day 1 to Month 4 after hospitalization, while the levels of GDF-15, osteopontin, syndecan-1, and syndecan-4 declined. At both time points, high levels of syndecan-1 were associated with microvascular obstruction, large infarct size, and reduced left ventricular ejection fraction, whereas high levels of syndecan-4 at Month 4 were associated with a higher myocardial salvage index and less dilatation of the left ventricle. Higher mortality rates were associated with periostin levels at both time points, low syndecan-4 levels at Month 4, or high GDF-15 levels at Month 4.
CONCLUSIONS
In patients with STEMI, we found an association between serum levels of ECM biomarkers and ischemic injury and mortality. The results provide new insight into the role ECM components play in ischemic injury following STEMI and suggests a potential for these biomarkers in prognostication after STEMI.
Topics: Humans; Male; Biomarkers; ST Elevation Myocardial Infarction; Female; Middle Aged; Aged; Extracellular Matrix; Myocardium; Osteopontin
PubMed: 38739599
DOI: 10.1371/journal.pone.0302732 -
CNS Neuroscience & Therapeutics May 2024A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the...
AIMS
A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear.
METHODS
We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in in vivo experiments.
RESULTS
Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. In vivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression.
CONCLUSION
Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.
Topics: Tumor Necrosis Factor-alpha; Pituitary Neoplasms; Humans; Adenoma; Neoplasm Invasiveness; Animals; Matrix Metalloproteinase 9; MAP Kinase Signaling System; Male; Cell Line, Tumor; Female; Mice; Mice, Nude; Autocrine Communication; Middle Aged; Bone Neoplasms; Adult; Rats; Cell Movement; Signal Transduction
PubMed: 38739004
DOI: 10.1111/cns.14749