Connective Tissue Research最新文献

{"title":"Impact of elevated serum advanced glycation end products and exercise on intact and injured murine tendons.","authors":"Shivam H Patel, Chad C Carroll","doi":"10.1080/03008207.2022.2135508","DOIUrl":"10.1080/03008207.2022.2135508","url":null,"abstract":"<p><strong>Overview: </strong>Delayed tendon healing is a significant clinical challenge for those with diabetes. We explored the role of advanced glycation end-products (AGEs), a protein modification present at elevated levels in serum of individuals with diabetes, on injured and intact tendons using a mouse model. Cell proliferation following tissue injury is a vital component of healing. Based on our previous work demonstrating that AGEs limit cell proliferation, we proposed that AGEs are responsible for the delayed healing process commonly observed in diabetic patients. Further, in pursuit of interventional strategies, we suggested that moderate treadmill exercise may support a healing environment in the presence of AGEs as exercise has been shown to stimulate cell proliferation in tendon tissue.</p><p><strong>Materials and methods: </strong>Mice began receiving daily intraperitoneal injections of bovine serum albumin (BSA)-Control or AGE-BSA injections (200μg/ml) at 16-weeks of age. A tendon injury was created in the central third of both patellar tendons. Animals assigned to an exercise group began a moderate treadmill protocol one week following injury. The intact Achilles tendon and soleus muscle were also evaluated to assess the effect of BSA and AGE-BSA on un-injured muscle and tendon.</p><p><strong>Results: </strong>We demonstrate that our injection dosing and schedule lead to an increase in serum AGEs. Our findings imply that AGEs indeed modulate gene expression following a patellar tendon injury and have modest effects on gene expression in intact muscle and tendon.</p><p><strong>Conclusions: </strong>While additional biomechanical analysis is warranted, these data suggest that elevated serum AGEs in persons with diabetes may impact tendon health.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"161-174"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of epigenetic modifications on bone remodeling in age-related osteoporosis.","authors":"Wenyue Yu,&nbsp;He-Ling Wang,&nbsp;Jianying Zhang,&nbsp;Chengcheng Yin","doi":"10.1080/03008207.2022.2120392","DOIUrl":"https://doi.org/10.1080/03008207.2022.2120392","url":null,"abstract":"<p><strong>Purpose: </strong>As the population ages, there is an increased risk of fracture and morbidity diseases associated with aging, such as age-related osteoporosis and other bone diseases linked to aging skeletons.</p><p><strong>Results: </strong>Several bone-related cells, including multipotent bone mesenchymal stem cells, osteoblasts that form bone tissue, and osteoclasts that break it down, are in symbiotic relationships throughout life. Growing evidence indicates that epigenetic modifications of cells caused by aging contribute to compromised bone remodeling and lead to osteoporosis. A number of epigenetic mechanisms are at play, including DNA/RNA modifications, histone modifications, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), as well as chromatin remodeling.</p><p><strong>Conclusion: </strong>In this review, we summarized the epigenetic modifications of different bone-related cells during the development and progression of osteoporosis associated with aging. Additionally, we described a compensatory recovery mechanism under epigenetic regulation that may lead to new strategies for regulating bone remodeling in age-related osteoporosis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"105-116"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncostatin M attenuates tumor necrosis factor-α-induced synthesis of macrophage-colony stimulating factor via suppression of Akt in osteoblasts.","authors":"Tomoyuki Hioki,&nbsp;Gen Kuroyanagi,&nbsp;Rie Matsushima-Nishiwaki,&nbsp;Osamu Kozawa,&nbsp;Haruhiko Tokuda","doi":"10.1080/03008207.2022.2109468","DOIUrl":"https://doi.org/10.1080/03008207.2022.2109468","url":null,"abstract":"<p><strong>Background: </strong>Oncostatin M produced by osteal macrophages, a cytokine that belongs to the interleukin-6 family, is implicated in bone fracture healing. Macrophage colony-stimulating factor (M-CSF) secreted from osteoblasts plays an important role in osteoclastogenesis. We have previously reported that tumor necrosis factor-α (TNF-α), a potent bone resorptive agent, stimulates the activation of p44/p42 mitogen-activated protein (MAP) kinase, Akt, and p70 S6 kinase in osteoblast-like MC3T3-E1 cells, and induces the synthesis of M-CSF at least in part via Akt.</p><p><strong>Objective: </strong>In the present study, we investigated whether oncostatin M affects the TNF-α-induced M-CSF synthesis in MC3T3-E1 cells and the underlying mechanisms.</p><p><strong>Methods: </strong>Clonal osteoblast-like MC3T3-E1 cells were treated with oncostatin M or rapamycin and then stimulated with TNF-α. M-CSF release was assessed by ELISA. M-CSF mRNA expression level was assessed by real-time RT-PCR. Phosphorylation of Akt, p44/p42 MAP kinase, and p70 S6 kinase was detected by Western blot analysis.</p><p><strong>Results: </strong>Oncostatin M dose-dependently reduced the TNF-α-stimulated M-CSF release. The expression of M-CSF mRNA induced by TNF-α was significantly suppressed by oncostatin M. Rapamycin, an inhibitor of mTOR/p70 S6 kinase, had little effect on the M-CSF release by TNF-α. Oncostatin M significantly reduced the TNF-α-induced phosphorylation of Akt and p44/p42 MAP kinase. However, the p70 S6 kinase phosphorylation by TNF-α was not affected by oncostatin M.</p><p><strong>Conclusion: </strong>These results strongly suggest that oncostatin M attenuates TNF-α-stimulated synthesis of M-CSF in osteoblasts, and the inhibitory effect is exerted at a point upstream of Akt and p44/p42 MAP kinase but not p70 S6 kinase.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"139-147"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative proteomics analysis of transforming growth factor-beta1-overexpressed human dental pulp stem cell-derived secretome on CD44-mediated fibroblast activation via canonical smad signal pathway.","authors":"H Salkin,&nbsp;M B Acar,&nbsp;Z B Gonen,&nbsp;K E Basaran,&nbsp;S Ozcan","doi":"10.1080/03008207.2022.2144733","DOIUrl":"https://doi.org/10.1080/03008207.2022.2144733","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study investigates whether the secretome collected from human dental pulp stem cells (hDPSCs) transfected with transforming growth factor-beta1 (TGF-β1) is related to CD44 expression of fibroblasts and canonical smad signaling pathway via proteomic analyzes.</p><p><strong>Materials and methods: </strong>In order to obtain secretome, hDPSCs were conditioned with serum-free alpha-MEM in an incubator containing 37°C, 5% CO₂, and humidity for 18-24 h. Proteins in control and TGF-β1 secretome were analyzed by tandem mass spectrometry-based shotgun proteomic method. Bioinformatic evaluations were completed via Ingenuity Pathway Analysis (IPA, QIAGEN) software. CD44 expressions in fibroblasts were evaluated by real time-PCR, western blot, and immunofluorescent staining. The relationship of canonical smad pathway and CD44 was analyzed by western blot and LC-MS/MS. Cell cycle, proliferation and wound healing tests were performed in the secretome groups.</p><p><strong>Results: </strong>Venn diagram was showed 174 common proteins were identified from each group. In the control secretome 140 unique proteins were identified and 66 entries were exclusive for TGF-β1 secretome. CD44 gene and protein expressions were increased in fibroblasts treated with TGF-β1 secretome. Relationship between targeted protein data showed that activation of the canonical TGF-β1/Smad pathway was up-regulated CD44 expression in fibroblasts. The canonical smad pathway-mediated upregulation of CD44 may increase the mitotic activity, proliferation, and wound healing potential in fibroblasts.</p><p><strong>Conclusion: </strong>While TGF-β1-transfected hDPSC secretome may be a potential therapeutic candidate in regenerative connective tissue therapies as it induces fibroblast activation, anti-TGF-β1-based therapies would be considered in histopathological conditions such as pulmonary fibrosis or hepatic fibrosis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"205-218"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9328487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sclerostin antibody promotes bone formation through the Wnt/β-catenin signaling pathway in femoral trochlear after patellar instability.","authors":"Chenyue Xu,&nbsp;Gang Ji,&nbsp;Xiaobo Chen,&nbsp;Lirong Yan,&nbsp;Tuwan Liang,&nbsp;Junle Liu,&nbsp;Fei Wang","doi":"10.1080/03008207.2022.2135507","DOIUrl":"https://doi.org/10.1080/03008207.2022.2135507","url":null,"abstract":"<p><strong>Purpose: </strong>The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab).</p><p><strong>Materials and methods: </strong>We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 µl), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, β-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson's trichrome staining were performed to evaluate cartilage changes.</p><p><strong>Results: </strong>PI increased the expression of SOST/sclerostin and RANKL, and decreased β-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation.</p><p><strong>Conclusions: </strong>SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/β-catenin signaling pathway in the femoral trochlear after PI.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"148-160"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9328478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting HDAC1 and promoting ER-α transcription.","authors":"Dawei Sun,&nbsp;Yuhui Chen,&nbsp;Xiaochun Liu,&nbsp;Guoying Huang,&nbsp;Guoyun Cheng,&nbsp;Chaoqun Yu,&nbsp;Jia Fang","doi":"10.1080/03008207.2022.2108415","DOIUrl":"https://doi.org/10.1080/03008207.2022.2108415","url":null,"abstract":"<p><strong>Objective: </strong>Metabolism is essential for bone development. The expressions of catabolic markers in chondrocytes show association with miR-34a-5p. This study discussed the mechanism by which miR-34a-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as well as bone metabolism.</p><p><strong>Methods: </strong>Expressions of BMSC surface markers were determined via flow cytometry. Osteogenic differentiation of BMSCs was subsequently induced. miR-34a-5p mimic, oe-HDAC1, or ER-α activator Ferutinin was introduced in BMSCs. Alkaline phosphatase activity and calcification were detected. Expressions of miR-34a-5p, HDAC1, ER-α, and osteogenic markers were determined via RT-qPCR and Western blot. The binding relationship between miR-34a-5p and HDAC1 was verified by a dual-luciferase assay. Mice at the age of 6 months and 18 months were assigned to the young group and age group for in vivo experiments, and aged mice were treated with agomiR miR-34a-5p. Expressions of serum miR-34a-5p, HDAC1, ER-α, and bone metabolism markers in mice were determined.</p><p><strong>Results: </strong>Osteogenic medium-induced BMSCs manifested increased expressions of miR-34a-5p and ER-α and decreased HDAC1 expression. miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs. miR-34a-5p targeted HDAC1. HDAC1 overexpression partially counteracted the promotional action of miR-34a-5p overexpression on osteogenic differentiation of BMSCs. miR-34a-5p overexpression activated ER-α. ER-α activator Ferutinin partially nullified the regulatory function of miR-34a-5p/HDAC1 on osteogenic differentiation of BMSCs. In vivo experiments showed that miR-34a-5p overexpression enhanced the potential of bone metabolism in aged mice.</p><p><strong>Conclusion: </strong>miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs and enhanced bone metabolism by promoting ER-α activation via targeting HDAC1.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"126-138"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin reduces myogenic contracture and myofibrosis induced by rat knee joint immobilization via AMPK-mediated inhibition of TGF-β1/Smad signaling pathway.","authors":"Feng Wang,&nbsp;Chen Xu Zhou,&nbsp;Zhi Zheng,&nbsp;Du Juan Li,&nbsp;Wen Li,&nbsp;Yun Zhou","doi":"10.1080/03008207.2022.2088365","DOIUrl":"https://doi.org/10.1080/03008207.2022.2088365","url":null,"abstract":"<p><strong>Purpose: </strong>The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-β) 1/Smad signaling pathway.</p><p><strong>Materials and methods: </strong>An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-β1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-β1/Smad signaling pathway.</p><p><strong>Results: </strong>We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-β1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-β1 and TGF-β1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-β1/Smad signaling pathway by metformin.</p><p><strong>Conclusion: </strong>Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-β1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 1","pages":"26-39"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of substance P on maintaining ligament homeostasis by inhibiting endochondral ossification during osteoarthritis progression.","authors":"Maya Tokumoto,&nbsp;Tomoyuki Nakasa,&nbsp;Yoshiko Shirakawa,&nbsp;Akinori Nekomoto,&nbsp;Yasunari Ikuta,&nbsp;Masakazu Ishikawa,&nbsp;Shigeru Miyaki,&nbsp;Nobuo Adachi","doi":"10.1080/03008207.2022.2099847","DOIUrl":"https://doi.org/10.1080/03008207.2022.2099847","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis (OA) is characterized by the degeneration of various tissues, including ligaments. However, pathological changes such as chondrogenesis and ossification in ligaments during OA are still unclear. Substance P (SP), a neuropeptide, has various functions including bone metabolism. This study aimed to analyze the expression and function of SP in OA ligaments, and the therapeutic potential of SP agonists in OA mice.</p><p><strong>Materials and methods: </strong>Expressions of SP, SOX9, and MMP13 were histologically analyzed in the posterior cruciate ligament (PCL) in humans with OA and Senescence-accelerated mouse-prone 8 (SAMP8) mice as a spontaneous OA model. The effect of SP agonists on chondrogenesis was evaluated using human ligament cells. Finally, SP agonists were administered intraperitoneally to destabilized medial meniscus (DMM) mice, and the PCL was histologically evaluated.</p><p><strong>Results: </strong>In PCL of humans and mice, the expression of SP, SOX9, and MMP13 was upregulated as OA progressed, but their expression was downregulated in severe degeneration. SP and SOX9 were co-expressed in chondrocyte-like cells. In ligament cells, SP agonists downregulated SOX9, RUNX2, and COL10A1. On evaluating chondrogenesis in ligament cells, pellet diameter was reduced in those treated with the SP agonists compared to those untreated. Administration of SP agonists ameliorated PCL degeneration in DMM mice. The Osteoarthritis Research Society and ligament scores in mice with SP agonists were significantly lower than those without SP agonists.</p><p><strong>Conclusions: </strong>SP plays an important role in maintaining ligament homeostasis by inhibiting endochondral ossification during OA progression. Targeting SP has therapeutic potential for preventing ligament degeneration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 1","pages":"82-92"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RANKL interferes with osteoclastogenesis in PEG-fused U937 cells through LGR4.","authors":"Juan A Arteaga,&nbsp;Carlos A Guerrero","doi":"10.1080/03008207.2022.2090350","DOIUrl":"https://doi.org/10.1080/03008207.2022.2090350","url":null,"abstract":"<p><strong>Introduction: </strong>RANKL plays an important role in the differentiation and maturation process of preosteoclast cells. The osteoclast is a multinucleated cell that can have various sizes and a variable number of nuclei. However, there are no models that allow us to understand how successive cell fusions have a limit, or how cell fusion is regulated.</p><p><strong>Methodology: </strong>The present investigation was aimed to determine whether fusing U937 cells with PEG to generate osteoclast-like cells expresses LGR4 and whether applying RANKL to these cells modifies osteoclastic activity compared to non-PEG-fused and RANKL-treated cells.</p><p><strong>Results: </strong>By fusing U937 cells with PEG, it was found that the LGR4 receptor expression was promoted as early as 24 hours of culture. Applying RANKL before or after fusion inhibits osteoclastic activity. Interfering RANKL interaction with LGR4 in PEG-treated cells recovers and increases cell fusion and osteoclastic activity. PEG-fused U937 cells show osteoclast markers similar to those observed in the classical RANKL-stimulated cell model.</p><p><strong>Conclusion: </strong>Our model allows us to understand that RANKL has fusogenic activity during the first days of culture and in fused cells modulates fusion, contributing to differentiate the role of RANKL before and after fusion through LGR4.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 1","pages":"40-52"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of simvastatin on osteogenesis of the extremity bones in aging rats.","authors":"Mengran Wang,&nbsp;Haowei Li,&nbsp;Jiaxin Tang,&nbsp;Yue Xi,&nbsp;Shiyi Chen,&nbsp;Ming Liu","doi":"10.1080/03008207.2022.2094790","DOIUrl":"https://doi.org/10.1080/03008207.2022.2094790","url":null,"abstract":"<p><strong>Purpose: </strong>Simvastatin is a prodrug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The main purpose of the current study is to assess the accurate function of simvastatin on osteoporosis of extremity bones in aging rats.</p><p><strong>Materials and methods: </strong>Fifty 15-month-old SD rats were divided into five groups (four simvastatin groups and one control group). The rats in four simvastatin groups were fed with different doses of simvastatin (5, 10, 20, and 40 mg/kg/d, respectively) for 3 months, whereas the rats in control group were fed the equal physiological saline. Calcium (Ca), phosphorus (P), and the lipid spectrum in serum were measured. Biochemical markers of bone metabolism, osteocalcin (OC), and tartrate-resistant acid phosphatase (Trap-5b), were analyzed using ELISA. The content of adipocytes in bone marrow was analyzed by histological staining. Finally, the bone quality of the femur and tibia were evaluated using dual-energy X-ray absorptiometry (DEXA), peri-quantity CT (pQCT), and the 3-point bending biomechanical test.</p><p><strong>Results: </strong>Simvastatin reduced serum triglycerides (TG), and 10 mg/kg/d of simvastatin significantly reduced the content of adipocytes in bone marrow compared to the control group. However, statistically significant differences between the simvastatin groups and the control group were not found in the CA, P, OC, Trap-5b, or the evaluation indexes of bone quality from DEXA, pQCT, and biomechanical tests.</p><p><strong>Conclusion: </strong>Simvastatin could not prevent osteoporosis of the extremity bones in aging rats.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 1","pages":"64-74"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}