Connective Tissue Research最新文献

{"title":"280 mT static magnetic field promotes the growth of postpartum condylar cartilage.","authors":"Yiwen Xiao,&nbsp;Qinhao Shen,&nbsp;Weihao Li,&nbsp;Yibo Zhang,&nbsp;Kang Yin,&nbsp;Yanhua Xu","doi":"10.1080/03008207.2022.2148527","DOIUrl":"https://doi.org/10.1080/03008207.2022.2148527","url":null,"abstract":"<p><strong>Purpose: </strong>Functional appliances made of permanent magnets have been used in jaw orthopedic treatment. However, whether the static magnetic field (SMF) generated by permanent magnets promotes the developmental sequence of condylar cartilage and thus promotes the growth of the mandible remains to be studied. The aim of this study was to investigate the effects of 280 mT SMF on postnatal condylar chondrogenesis and endochondral ossification and the roles of FLRT3, FGF2 and BMP2 signaling in this chondrodevelopmental sequences.</p><p><strong>Methods: </strong>Forty-eight rats were assigned to two groups (control and SMF). The condyles were collected at the specified time points. The histomorphological changes in the condyle were observed by histological staining. The expression of proteins related to the proliferation and differentiation of the condylar cartilage and the changes in subchondral bone microstructure were analyzed by immunohistochemical staining and micro-CT scanning. FLRT3, FGF2, and BMP2 expression was detected by immunofluorescence staining.</p><p><strong>Results: </strong>Under SMF stimulation, the cartilage of young rats grew longitudinally and laterally, and the thickness of the cartilage became thinner as it grew. The SMF promoted the proliferation and differentiation of condylar chondrocytes and endochondral ossification and increased subchondral bone mineral density, and BMP2 signaling was involved. Moreover, under SMF loading, the increased expression of FGF2 and FLRT3 were involved in regulating cartilage morphogenesis and growth. In late development, the decreased expression of FGF2/FLRT3 and the increased expression of BMP2 promoted endochondral ossification. The SMF accelerated this opposite expression trend.</p><p><strong>Conclusion: </strong>FGF2/FLRT3 and BMP2 signals are involved in the regulatory effect of SMF exposure on chondrogenesis and endochondral ossification, which provides a theoretical basis for the clinical use of magnetic appliances to promote condylar growth.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542729","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":"Tendon properties in a mouse model of severe osteogenesis imperfecta.","authors":"Larissa Sinkam,&nbsp;Iris Boraschi-Diaz,&nbsp;René B Svensson,&nbsp;Michael Kjaer,&nbsp;Svetlana V Komarova,&nbsp;Raynald Bergeron,&nbsp;Frank Rauch,&nbsp;Louis-Nicolas Veilleux","doi":"10.1080/03008207.2022.2161376","DOIUrl":"https://doi.org/10.1080/03008207.2022.2161376","url":null,"abstract":"<p><strong>Purpose/aim of the study: </strong>Osteogenesis imperfecta is a heritable bone disorder that is usually caused by mutations in collagen type I encoding genes. The impact of such mutations on tendons, a structure with high collagen type I content, remains largely unexplored. We hypothesized that tendon properties are abnormal in the context of a mutation affecting collagen type I. The main purpose of the study was to assess the anatomical, mechanical, and material tendon properties of <i>Col1a1</i>^<i>Jrt/+</i> mice, a model of severe dominant OI.</p><p><strong>Materials and methods: </strong>The Flexor Digitorum Longus (FDL) tendon of <i>Col1a1</i>^<i>Jrt/+</i> mice and wild-type littermates (WT) was assessed with in vitro mechanical testing.</p><p><strong>Results: </strong>The results showed that width and thickness of FDL tendons were about 40% larger in WT <i>(p < 0.01)</i> than in <i>Col1a1</i>^<i>Jrt/+</i> mice, whereas the cross-sectional area was 138% larger <i>(p < 0.001)</i>. The stiffness, peak- and yield-force were between 160% and 194% higher in WT vs. <i>Col1a1</i>^<i>Jrt/+</i> mice. The material properties did not show significant differences between mouse strains with differences <15% between WT and <i>Col1a1</i>^<i>Jrt/+</i> <i>(p > 0.05)</i>. Analysis of the Achilles tendon collagen showed no difference between mice strains for the content but collagen solubility in acetic acid was 66% higher in <i>WT</i> than in <i>Col1a1</i>^<i>Jrt/+</i> (p < 0.001).</p><p><strong>Conclusions: </strong>This study shows that the FDL tendon of <i>Col1a1</i>^<i>Jrt/+</i> mice has reduced mechanical properties but apparently normal material properties. It remains unclear whether the tendon phenotype of <i>Col1a1</i>^<i>Jrt/+</i> mice is secondary to muscle weakness or a direct effect of the <i>Col1a1</i> mutation or a combination of both.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9481768","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":"Recent progress in the biology and physiology of BMP-8a.","authors":"Jiawei Tang,&nbsp;Miao Tan,&nbsp;Siqi Liao,&nbsp;Mengwei Pang,&nbsp;Jie Li","doi":"10.1080/03008207.2022.2160326","DOIUrl":"https://doi.org/10.1080/03008207.2022.2160326","url":null,"abstract":"<p><strong>Purpose: </strong>BMP-8a is a member of bone morphogenetic proteins (BMPs) and plays a regulatory role in human growth and development as a transcription regulator. This review aims to summarize the current research on the impact and mechanism of BMP-8a in female and male reproduction, formation and eruption of teeth, bone and cartilage development, tissue differentiation, disease occurrence, progression and prognosis.</p><p><strong>Methods: </strong>The phrases \"BMP-8a,\" \"BMPs,\" \"regulator,\" \"mechanism,\" \"osteoblast,\" \"cartilage,\" \"cancer,\" \"disease,\" and \"inflammation\" were searched in the PubMed database. The abstracts were evaluated, and a series of original publications and reviews were examined.</p><p><strong>Results: </strong>According to the search, BMP-8a affects the development of the uterus by inhibiting luteinization and plays an important role in late spermatogenesis. It is highly expressed in osteogenesis and differentially expressed in chondrogenesis. Furthermore, BMP-8a has a significant impact on the occurrence, development and prognosis of various diseases.</p><p><strong>Conclusions: </strong>BMP-8a regulates important factors and pathways, such as SMAD2/3 and SMAD1/5/8, to promote or inhibit the developmental processes of human reproductive organs. BMP-8a is also a member of the BMP family of proteins that regulates chondrogenesis and osteogenesis. In addition to its osteoinductive capabilities, BMP-8a is involved in the progression of diverse cancers.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488526","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":"Dependence of crack shape in loaded articular cartilage on the collagenous structure.","authors":"Yasir Al-Saffar,&nbsp;Eng Kuan Moo,&nbsp;Belinda Pingguan-Murphy,&nbsp;John Matyas,&nbsp;Rami K Korhonen,&nbsp;Walter Herzog","doi":"10.1080/03008207.2023.2166500","DOIUrl":"https://doi.org/10.1080/03008207.2023.2166500","url":null,"abstract":"<p><p>Cartilage cracks disrupt tissue mechanics, alter cell mechanobiology, and often trigger tissue degeneration. Yet, some tissue cracks heal spontaneously. A primary factor determining the fate of tissue cracks is the compression-induced mechanics, specifically whether a crack opens or closes when loaded. Crack deformation is thought to be affected by tissue structure, which can be probed by quantitative polarized light microscopy (PLM). It is unclear how the PLM measures are related to deformed crack morphology. Here, we investigated the relationship between PLM-derived cartilage structure and mechanical behavior of tissue cracks by testing if PLM-derived structural measures correlated with crack morphology in mechanically indented cartilages.</p><p><strong>Methods: </strong>Knee joint cartilages harvested from mature and immature animals were used for their distinct collagenous fibrous structure and composition. The cartilages were cut through thickness, indented over the cracked region, and processed histologically. Sample-specific birefringence was quantified as two-dimensional (2D) maps of azimuth and retardance, two measures related to local orientation and degree of alignment of the collagen fibers, respectively. The shape of mechanically indented tissue cracks, measured as depth-dependent crack opening, were compared with azimuth, retardance, or \"PLM index,\" a new parameter derived by combining azimuth and retardance.</p><p><strong>Results: </strong>Of the three parameters, only the PLM index consistently correlated with the crack shape in immature and mature tissues.</p><p><strong>Conclusion: </strong>In conclusion, we identified the relative roles of azimuth and retardance on the deformation of tissue cracks, with azimuth playing the dominant role. The applicability of the PLM index should be tested in future studies using naturally-occurring tissue cracks.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859489","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":"Early patellofemoral cartilage and bone pathology in a rat model of noninvasive anterior cruciate ligament rupture.","authors":"Mackenzie M Fleischer,&nbsp;Samantha E Hartner,&nbsp;Michael D Newton,&nbsp;Kevin C Baker,&nbsp;Tristan Maerz","doi":"10.1080/03008207.2022.2136571","DOIUrl":"10.1080/03008207.2022.2136571","url":null,"abstract":"<p><strong>Objective: </strong>Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model.</p><p><strong>Methods: </strong>Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion.</p><p><strong>Results: </strong>Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea.</p><p><strong>Conclusion: </strong>The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329167","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 effects of the amount of weight bearing on articular cartilage early after ACL reconstruction in rats.","authors":"Akinori Kaneguchi,&nbsp;Kaoru Yamaoka,&nbsp;Junya Ozawa","doi":"10.1080/03008207.2022.2141627","DOIUrl":"https://doi.org/10.1080/03008207.2022.2141627","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis that develops after anterior cruciate ligament (ACL) reconstruction is a critical issue. We examined the effects of the amount of weight bearing early after ACL reconstruction on articular cartilage.</p><p><strong>Materials and methods: </strong>Rats were divided into groups according to the treatment received: untreated control, ACL reconstruction (ACLR), ACL reconstruction plus hindlimb unloading (ACLR + HU), and ACL reconstruction plus morphine administration (ACLR + M). ACL reconstruction was performed on the right knee throughout the groups. To assess the amount of weight bearing, one-hindlimb standing time ratio (STR; operated side/contralateral side) during treadmill locomotion was evaluated during the experimental period. At day 7 or 14 post-surgery, cartilage degeneration of the medial tibial plateau was histologically assessed.</p><p><strong>Results: </strong>In the ACLR group, reduction in weight bearing characterized by significantly reduced STR was observed between day 1 and 7. Reduction in weight bearing was partially attenuated by morphine administration. Compared with the control group, the ACLR group exhibited an increased Mankin score that was accompanied by increased cyclooxygenase-2 expression in the anterior region. In the ACLR + HU group, Mankin scores were significantly higher in the middle and posterior regions, and cartilage thickness in these regions was significantly thinner than those in the ACLR group. In the ACLR + M group, although chondrocyte density in the anterior region was increased, all other parameters were not significantly different from those in the ACLR group.</p><p><strong>Conclusions: </strong>Our results suggest that early weight bearing after ACL reconstruction is important to reduce cartilage degeneration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327802","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":"Genome-wide association study of handgrip strength in the Northern Chinese adult twins.","authors":"Jia Luo,&nbsp;Tianhao Zhang,&nbsp;Weijing Wang,&nbsp;Dongfeng Zhang","doi":"10.1080/03008207.2022.2104160","DOIUrl":"https://doi.org/10.1080/03008207.2022.2104160","url":null,"abstract":"<p><strong>Purpose: </strong>Currently, new loci related to handgrip strength have been identified in genome-wide association studies. However, this topic is an understudied area in the Chinese population.</p><p><strong>Materials and methods: </strong>A total of 135 dizygotic twin pairs recruited from the Qingdao Twin Registry system were included in the present study. Using GEMMA, VEAGSE2, and PASCAL software for SNP-based analysis, gene-based analysis, and pathway-based analysis, respectively. The resulting SNPs were subjected to eQTL analysis.</p><p><strong>Results: </strong>Although none of the loci reach the statistically significant level (<i>p</i> < 5 × 10^-8), we found 19 SNPs exceeding the suggestive significant level (<i>p</i> < 1 × 10^-5). After imputation, 162 SNPs reached suggestive evidence level for handgrip strength. A total of 1,118 genes reached the nominal significance level (<i>p</i> < 0.05) in gene-based analysis. A total of 626 potential biological pathways were associated with handgrip strength (<i>p</i> < 0.05). The results of eQTL analysis were mainly enriched in tissues such as the muscle-skeletal, brain, visceral fat, and brain-cortical.</p><p><strong>Conclusions: </strong>Genetic variants may involve in regulatory domains, functional genes, and biological pathways that mediate handgrip strength.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327299","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}