Parathyroid hormone (1-34) retards the lumbar facet joint degeneration and activates Wnt/ß-catenin signaling pathway in ovariectomized rats.

PURPOSE: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1-34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1-34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease. METHODS: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1-34) or 17ß-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/ß-catenin signaling activity in the cartilage and subchondral bone of the L4-L5 FJs and serum biomarkers were analyzed. RESULTS: Administration of PTH (1-34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1-34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1-34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and ß-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1-34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/ß-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/ß-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status. CONCLUSION: Wnt/ß-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1-34) is effective in treating this disease with better efficacy than 17ß-estradiol, and the efficacy may be attributed to its restoration of Wnt/ß-catenin signaling.

Targeting JUNB to modulate M2 macrophage polarization in preeclampsia.

Preeclampsia (PE) is a complex disorder affecting pregnant women, leading to significant maternal and fetal morbidity and mortality. Understanding the cellular dynamics and molecular mechanisms underlying PE is crucial for developing effective therapeutic strategies. This study utilized single-cell RNA sequencing (scRNA-seq) to delineate the cellular landscape of the placenta in PE, identifying 11 distinct cell subpopulations, with macrophages playing a pivotal role in mediating cell-cell communication. Specifically, the transcription factor JUNB was found to be a key gene in macrophages from PE samples, influencing the interaction between macrophages and both epithelial and endothelial cells. Functional experiments indicated that interference with JUNB expression promoted macrophage polarization towards an M2 phenotype, which facilitated trophoblast invasion, migration, and angiogenesis. Mechanistically, JUNB regulated the MIIP/PI3K/AKT pathway, as evidenced by gene expression analysis following JUNB knockdown. The study further demonstrated that targeting JUNB could activate the PI3K/AKT pathway by transcriptionally activating MIIP, thus promoting M2 polarization and potentially delaying the onset of PE. These findings present new insights into the pathogenesis of PE and suggest a novel therapeutic approach by modulating macrophage polarization.

Pollution characteristics and prospective risk of microplastics in the Zhengzhou section of Yellow River, China.

The ubiquitous occurrence of microplastics (MPs) in the freshwater has attracted widespread attention. The Zhengzhou section of the Yellow River was the most prosperous region in ancient China, and the rapid urbanization, industrialization, and agricultural practices contributed to MPs pollution in aquatic systems recently, whereas the contamination status of MPs in the area is still not available. In this study, a total of fourteen sampling cross-sections were selected in the region to collect water samples systematically for the analysis of MPs pollution characteristics and potential risks. Results showed that abundance of MPs in the water were ranged from 2.33 to 15.50 n/L, with an average value of 6.40 ± 3.40 n/L, which was higher than it in other inland rivers from China. Moreover, the MPs of 0.5-2 mm were the dominant sizes in Yellow River of Zhengzhou region, and most of them were black fibres. The top three polymers were Polyethylene terephthalate (PET), Polyamide (PA) and Polypropylene (PP). High diversity indices of MPs observed at S3, S4, S5, S6, S7, and S8 for size, colour, polymer and shape indicated diverse and complex sources of MPs in those cross-sections. The MPs in water from Zhengzhou area of Yellow River probably degraded from textiles, fishing net, plastic bags, mulching film, packaging bags, and tire wear. The chemical risk assessment revealed a level III risk for study area, while S8 and S11 in which PVA or PAN with higher hazard score detected were categorised as class V risk. Coincidentally, probabilistic risk assessment showed a considerable ecological risk of MPs from Yellow River in Zhengzhou City, with possibility of 99.48 and 98.01 % adverse effect for food dilution and translocation-mediated mechanism, respectively. The results are expected to assistance for development of policies and ultimately combating MPs pollution.

[Occurrence Characteristic and Risk Assessment of Microplastics in Sishui River (Xingyang Section)].

Urban rivers are the main receptors and transporters of microplastic pollution. Understanding the occurrence and environmental risk of microplastics in urban rivers can provide theoretical basis for further control of microplastic pollution. The Sishui River, a tributary of the Yellow River, was selected as the research object. A total of nine water samples were collected from sewage outlets of the Sishui River (Xingyang section). The microplastics in the collected samples were characterized by their sizes, shapes, and colors using a microscope. It was found that microplastics were mostly in the form of transparent fibers and fragments in the water body of sewage outlets, of which the size below 500 µm was relatively high. In addition, PET and PE polymers were identified as the main types using a laser infrared imager. The correlation analysis showed that there was a significant correlation between the PET and PE, indicating that they were similar in origin. The results of the environmental risk assessment showed that the type of microplastics was the main factor affecting the assessment results, whereas the risk values of six sewage samples containing PVC were high. However, the value of pollution load index revealed a low risk level of pollutants in the study area.

3D printed PLGA/MgO/PDA composite scaffold by low-temperature deposition manufacturing for bone tissue engineering applications.

Introduction: Bones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. Methods: PLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions. Results: The prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation. Conclusion: Low-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.

Estrogen deficiency impedes fracture healing despite eliminating the excessive absorption of the posterior callus in a semi-fixed distal tibial fracture mouse model.

BACKGROUND: Treatment of distal tibial fractures is a challenge due to their specific anatomical location. However, there is no appropriate mouse model to simulate a clinical distal tibial fracture for basic research. The aim of this investigation was to evaluate the feasibility of simulating a clinical fracture of the distal tibia of mice and to investigate the effect of ovariectomy (OVX)-induced osteoporosis on fracture healing in this model. METHODS: Sixty female 8-week-old C57BL/6 mice were randomly divided into two groups, either sham or OVX. A semi-fixation distal tibia fracture was established in the right tibia after 8 weeks of OVX. The right tibias were collected at 7, 14, 21, and 28 days post fracture. RESULTS: In the semi-fixation distal tibia fracture model, the posterior callus in the sham group showed excessive bone resorption and lower bone mass phenotype compared with the anterior site; a similar trend was not found in the OVX group. At 28 days post fracture, the posterior callus was more mineralized than the anterior callus in the OVX group. Although the fracture healing of the sham group showed a special phenotype in this mode, the progress and quality of fracture healing were still better than those of the OVX group. CONCLUSION: A semi-fixed distal tibial closed fracture mouse model was successfully established. In this model, excess bone resorption of the posterior callus impaired normal fracture healing, but not in OVX-induced osteoporotic bone. Although the stress shielding effect was not observed in the OVX group, impaired bone healing caused by OVX was still present. Our results suggest that this fracture model may have potential for studies on distal tibial fractures and stress shielding.

A decreased number of circulating regulatory T cells is associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: As an autoimmune disease affecting women of reproductive age, systemic lupus erythematosus (SLE) is linked to adverse fetal and maternal outcomes. However, the status of peripheral lymphocytes in SLE patients with different pregnancy outcomes is unclear. This retrospective cross-sectional study explored the relationship between lymphocyte subpopulations and pregnancy outcomes in married SLE female patients. METHODS: The absolute numbers of peripheral T, helper T (Th)1, Th2, Th17, regulatory T (Treg), B, and natural killer (NK) cell subpopulations from 585 female SLE patients and 91 female healthy controls (HCs) were assessed. We compared the lymphocyte subpopulations in SLE patients with HCs and analyzed the absolute number and ratio of Treg cells according to pregnancy outcome in SLE patients. RESULTS: SLE patients had decreased numbers of T, B, NK, Th1, Th2, Th17, and Treg cells and an imbalance in pro- and anti-inflammatory cells (p < .05), as well as adverse pregnancy outcomes. In abortion patients, the number of Treg cells (p = .008) decreased, leading to an imbalance in effector T and Treg cells. The ratio of Treg cells was higher in SLE patients with nulliparity than in those with one or two parities. CONCLUSIONS: The absolute numbers of lymphocyte subpopulations in SLE patients decreased, which was associated with abortion and parity (p < .05). These results suggest that a loss of immune tolerance mediated by Tregs triggers pregnancy loss.

Chemical looping steam reforming of glycerol for hydrogen production over NiO-Fe2O3/Al2O3 oxygen carriers.

Fe-based oxygen carriers (OCs) are widely used in chemical looping steam reforming (CLSR) due to excellent resistance to carbon buildup, low toxicity, and high activity. In this study, a type of nano NiO-Fe2O3/Al2O3 Fe-based OC that can easily be reduced by fuels and re-oxidized by air was developed for use in glycerol CLSR. It was synthesized by co-precipitation and impregnation. Based on the quadratic regression orthogonal model, a quadratic polynomial function was established to investigate the effects of temperature (T), water/carbon ratio (S/C), and loading (M) on hydrogen content (HL) and hydrogen selectivity (S). The OCs were characterized by XRD, XPS, SEM/EDX-mapping, TEM, and H2-TPR to determine their physicochemical properties. XPS shows the Fe phase highly interacted with the Al2O3 supporting matrix by forming Fe aluminates in NiO-Fe2O3/Al2O3. The S (85.33%) and HL (78.41%) were obtained under the optimal conditions T = 600 °C, S/C = 1.0 mol mol-1 and M = 0. A hydrogen content fluctuation within 4% was obtained under T = 700 °C, S/C = 1.0 mol mol-1, and M = 2.5%, which means the cycle stability is perfect because of the addition of Ni. This study provides a basis for the development of efficient oxygen carriers in the CLSR system.

Differential expression of HAVCR2 gene in pan-cancer: A potential biomarker for survival and immunotherapy.

T-cell immunoglobulin mucin 3 (TIM-3) has emerged as a promising immune checkpoint target in cancer therapy. However, the profile of the hepatitis A virus cellular receptor 2 (HAVCR2) gene, encoding TIM-3 expression, is still obscure, along with its role in cancer immunity and prognosis. This study comprehensively analyzed HAVCR2 expression patterns in pan-cancer and underlined its potential value for immune checkpoint inhibitor-based immunotherapy. Our results displayed that HAVCR2 was differentially expressed and closely corresponded to survival status in pan-cancer. More importantly, the HAVCR2 expression level was also significantly related to cancer immune infiltration, immune checkpoint genes, and immune marker genes. Enrichment analyses implicated HAVCR2-associated terms in cancer, including immunity, metabolism, and inflammation. Our study demonstrated that HAVCR2 could participate in differing degrees of immune infiltration in tumorigenesis. The highlights of the HAVCR2 pathway revealed that TIM-3 could function as both a biomarker and clinical target to improve the therapeutic efficacy of immunotherapy.

A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy.

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear. Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan-Meier method (univariate Cox regression analysis and Kaplan-Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman's rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal-Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level. Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman's rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways. Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.

Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.

Enhanced photocatalytic hydrogen evolution and ammonia sensitivity of double-heterojunction g-C3N4/TiO2/CuO.

The performance of semiconductor photocatalysts has been limited by rapid electron-hole recombination. One strategy to overcome this problem is to construct a heterojunction structure to improve the survival rate of electrons. In this context, a novel g-C3N4/TiO2/CuO double-heterojunction photocatalyst was developed and characterized. Its photocatalytic activity for hydrogen production from water-methanol photocatalytic reforming was explored. Methanol is always used to eliminate semiconductor holes. The g-C3N4/TiO2/CuO double-heterojunction photocatalyst with a narrow bandgap of ∼1.38 eV presented excellent photocatalytic activity for hydrogen evolution (97.48 µmol (g h)-1) under visible light irradiation. Compared with g-C3N4/TiO2 and CuO/TiO2, the photocatalytic activity of g-C3N4/TiO2/CuO for hydrogen production was increased approximately 7.6 times and 1.8 times, respectively. Below 240 °C, the sensitivity of g-C3N4/TiO2/CuO to ammonia was approximately 90% and 46% higher than that of g-C3N4/TiO2 and CuO/TiO2, respectively. The enhancement of the photocatalytic activity and gas sensing properties of the g-C3N4/TiO2/CuO composite resulted from the close interface contact established by the double heterostructure. The trajectory of electrons in the double heterojunction conformed to the S-scheme. UV-vis, PL, and transient photocurrent characterization showed that the double heterostructure effectively inhibited the recombination of e-/h+ pairs and enhanced the migration of photogenerated electrons.

The combined anti-osteoporotic effects of simvastatin and exercise in ovariectomized mice fed a high-fat diet.

BACKGROUND: To evaluate and compare the effects of the combined intervention of simvastatin and exercise on the bone degeneration in a mice model of osteoporosis (OP) induced by obesity and estrogen deficiency. METHODS: 56 female 3-month-old C57BL/6 mice were given a standard diet or a high-fat diet after ovariectomy (OVX) or sham surgery. Drug administration and exercise training were initiated 72 h after surgical operation, which were treated with simvastatin (10 mg/kg/day) or exercise (15 m/min for 30 min/day) or combined with simvastatin and exercise at 72 h for 8 weeks. The pathology of OP was assessed by histomorphology analyses, immunohistochemistry (IHC), micro-computed tomography (Micro-CT), enzyme-linked immunosorbent assay (ELISA) and cell culture. RESULTS: The coexistence of obesity and estrogen deficiency significantly further exacerbated OP pathology, and combined intervention showed a better significant anti-osteoporosis effect than monotherapy. In details, simvastatin combined with exercise ameliorated the abnormal bone mass, microstructure and bone marrow adipocyte differentiation, significantly increased osteoprotegerin (OPG), type 1 collagen (Col-I), RUNX2 and osteocalcin (OCN) expression, decreased the expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and peroxisome proliferator-activated receptor γ (PPARγ). Furthermore, combined intervention markedly improved abnormal metabolic status, reduced the levels of serum glucose, insulin, triglycerides (TG), low-density lipoprotein (LDL), leptin, CTX-1 and IL-1ß, and increased the level of OCN. CONCLUSIONS: The coexistence of obesity and estrogen deficiency further aggravates bone tissue degeneration and abnormal metabolic pathology, which could be better inhibited by the combination with simvastatin and exercise instead of single intervention, suggesting that combined intervention may be a potential candidate for amelioration of the progression of OP.

Combination of metformin and exercise alleviates osteoarthritis in ovariectomized mice fed a high-fat diet.

OBJECTIVE: To evaluate and compare the effects of the combined intervention of metformin and exercise on the degeneration of cartilage and subchondral bone in a mouse model of osteoarthritis (OA) induced by estrogen deficiency and obesity. METHODS: 56 female 3-month-old C57BL/6 mice underwent ovariectomy (OVX) (n = 40) or a sham operation (n = 16) and were randomized into seven groups (n = 8/group): 1) sham-operated mice with a normal diet (Sham), 2) OVX mice with a normal diet (OVX), 3) sham-operated mice with high-fat diet (HFD) (HSVX), 4) OVX mice with HFD (HOVX), 5) OVX mice with HFD + exercise (HOVE), 6) OVX mice with HFD + metformin (HOMX), and 7) OVX mice with HFD + metformin + exercise (HOME). Drug administration and exercise training were initiated 72 h after surgical operation. The pathology of OA was assessed by histomorphology analyses, immunohistochemistry (IHC), tartrate-resistant acid phosphatase (TRAP) staining, micro-computed tomography and enzyme-linked immunosorbent assay (ELISA). RESULTS: Histomorphological analysis revealed that OA was significantly exacerbated by the coexistence of estrogen deficiency and obesity and markedly alleviated by the combined intervention. In details, metformin plus exercise ameliorated the abnormal metabolic status and cartilage lesions, significantly increased aggrecan and collagen-II expression and decreased the expression of ADAMTS-4. Furthermore, combined intervention markedly improved bone degeneration, bone mass and microarchitecture of subchondral bone. And the intervention also increased the concentration of OCN and decreased the serum concentration of IL-1ß and CTX-1 and glucose. CONCLUSIONS: The coexistence of estrogen deficiency and obesity further aggravates abnormal metabolic pathology and articular degeneration, which could be prevented by the combination with metformin and exercise, suggesting that combined intervention may be a potential candidate for amelioration of the progression of OA.

Protective Effect of Alendronate on Lumbar Facet Degeneration in Ovariectomized Rats.

BACKGROUND Facet joint degeneration (FJD) is a potential source of lower back pain, and estrogen deficiency can accelerate FJD. The present study aimed to investigate the effects of alendronate (ALN) on FJD induced by ovariectomy (OVX) in rats. MATERIAL AND METHODS Thirty female Sprague-Dawley rats underwent either bilateral OVX (n=20) or sham surgery (n=10). The OVX rats subsequently received either subcutaneous ALN (70 µg/kg/week) or vehicle for 12 weeks. Subchondral bone mass and microarchitecture were evaluated by micro-computed tomography. Cartilage degradation was evaluated by toluidine blue staining and histological scoring. RESULTS Compared with the Sham group, the OVX group had significantly decreased bone mineral density, bone volume/trabecular volume, and trabecular thickness, significantly increased trabecular separation in subchondral bone, and significantly higher histological score for cartilage degeneration, particularly loss of cartilage thickness. ALN treatment significantly reversed the changes in subchondral bone, preserved cartilage thickness, and reduced the histological score. Immunohistochemical analyses showed significantly decreased expression of ADAMTS-4, MMP-13, and caspase-3 in the OVX+ALN group compared with the OVX group. CONCLUSIONS Treatment with ALN suppressed bone loss, subchondral bone architecture deterioration, and cartilage degeneration in OVX rats, which can be explained by roles of ALN in preservation of subchondral bone mass and microarchitecture, and counteraction of catabolism and chondrocyte apoptosis in cartilage.

Salmon calcitonin exerts better preventive effects than celecoxib on lumbar facet joint degeneration and long-term tactile allodynia in rats.

OBJECTIVE: To evaluate and compare the effects of salmon calcitonin (sCT) and celecoxib (CLX) on cartilage, subchondral bone and tactile allodynia in a rat model of lumbar facet joint (FJ) osteoarthritis (OA). METHOD: Forty 3-month-old male Sprague-Dawley rats were randomly divided into four groups: 30 received surgical collagenase (type II) injections in the right L3-L6 facet joints followed by 8 weeks of treatment with normal saline, CLX or sCT, and the other 10 received sham surgery. Tactile allodynia, changes of cartilage and subchondral bone of the L4-L5 FJs, and serum biomarkers were analyzed for all rats. RESULTS: Both sCT and CLX ameliorated cartilage lesions, significantly increased aggrecan expression and decreased caspase-3 expression. sCT also decreased the expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4). According to the micro-computed tomography (micro-CT) analysis, sCT significantly improved microarchitecture parameters of subchondral bone and micro-CT score; and inhibited articular process hypertrophy. CLX showed better antihyperalgesic effects than sCT on days 3 and 7 postoperatively despite no statistical differences, whereas sCT possessed better analgesic effects than CLX on days 42 and 56. Besides, the sCT treatment reduced the elevated cartilage oligomeric matrix protein (COMP) concentration in rats injected with collagenase (type II). CONCLUSIONS: Both sCT and CLX exerted preventive effects on FJ OA caused by collagenase (type II), but sCT showed more protective effects, particularly on maintaining cartilage metabolism, restraining the deterioration of the subchondral bone microarchitecture and tactile allodynia, and reducing serum COMP concentrations.

Salmon Calcitonin Attenuates Degenerative Changes in Cartilage and Subchondral Bone in Lumbar Facet Joint in an Experimental Rat Model.

BACKGROUND Facet joint degeneration (FJD) is one of the common causes of low back pain (LBP), and estrogen deficiency is one of the triggers for FJD. Calcitonin may possess the potential for treating osteoarthritis, but to date the hormone has not been studied in the treatment of FJD. Therefore, the aim of this study was to investigate the effects of salmon calcitonin (sCT) on FJD induced by estrogen deficiency after ovariectomy (OVX). MATERIAL AND METHODS Thirty female Sprague-Dawley rats were randomly assigned to 3 groups: the OVX group received bilateral OVX, the OVX + sCT group received subcutaneous administration of sCT (16 IU/kg/2 days) following bilateral OVX, and the Sham group received sham surgery. All rats were euthanized at 12 weeks post-OVX. Serum COMP level, cartilage degradation, and subchondral bone micro-architecture were evaluated. RESULTS sCT relieved cartilage surface lesions, reduced histological score, and significantly increased cartilage thickness. The OVX + sCT group exhibited significantly increased expression of aggrecan, as well as significantly decreased levels of ADAMTS-4, MMP-13, and caspase-3. The results of micro-computed tomography analysis revealed that the OVX + sCT group exhibited higher BMD, BV/TV, and Tb.Th values but a lower Tb.Sp value than that of the OVX group. Serum COMP concentrations were significantly correlated with histological score and cartilage thickness. CONCLUSIONS sCT can inhibit the progression of FJD in OVX rats, which is attributed to its inhibitory effects on cartilage metabolism imbalance, chondrocyte apoptosis, and subchondral bone remodeling. Serum COMP has diagnostic potential for FJD.