Qin Zhang, Ying Yuan, Bin Wang, Ping Gong, Lin Xiang
{"title":"Lysophosphatidic acid regulates implant osseointegration in murine models via YAP.","authors":"Qin Zhang, Ying Yuan, Bin Wang, Ping Gong, Lin Xiang","doi":"10.1080/03008207.2025.2459856","DOIUrl":"10.1080/03008207.2025.2459856","url":null,"abstract":"<p><strong>Background: </strong>Lysophosphatidic acid (LPA), a simple bioactive lysophospholipid, has been reported to regulate bone homeostasis and bone remodeling. This study aimed to elucidate the function and intrinsic mechanism of LPA in osseointegration in murine models.</p><p><strong>Method: </strong>We constructed immediate implant models in murine maxillae. Micro-CT, H&E staining, and PCR assays were performed to evaluate the effects of LPA on osseointegration. Furthermore, <i>Prx1-Cre;Yap<sup>f/f</sup></i> mice and <i>Sp7-Cre;Yap<sup>f/f</sup></i> mice were generated to investigate the role of YAP on LPA-induced osseointegration.</p><p><strong>Result: </strong>In this study, we identified that LPA might promote bone deposition on the tissue-implant interface and improve osseointegration. In addition, conditional knockout of YAP from MCSs and pre-osteoblasts blunts LPA-induced osteogenesis and osseointegration in mice.</p><p><strong>Conclusion: </strong>Our data demonstrated that LPA-YAP signaling is particularly important to regulate osseointegration, which expands our understanding of LPA and provide the potential of LPA to be used in osseointegration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"87-95"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187674","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}
LeeAnn A Hold, Tessa Phillips, Paige Cordts, Stephanie S Steltzer, Seung-Ho Bae, Brandon W Henry, Nicole Migotsky, Sydney Grossman, Cynthia Dela Cruz, Vasantha Padmanabhan, Molly B Moravek, Ariella Shikanov, Adam C Abraham, Megan L Killian
{"title":"Functional changes to Achilles tendon and enthesis in an adolescent mouse model of testosterone hormone therapy.","authors":"LeeAnn A Hold, Tessa Phillips, Paige Cordts, Stephanie S Steltzer, Seung-Ho Bae, Brandon W Henry, Nicole Migotsky, Sydney Grossman, Cynthia Dela Cruz, Vasantha Padmanabhan, Molly B Moravek, Ariella Shikanov, Adam C Abraham, Megan L Killian","doi":"10.1080/03008207.2025.2465322","DOIUrl":"10.1080/03008207.2025.2465322","url":null,"abstract":"<p><strong>Purpose/aim: </strong>Some youth seek puberty suppression to prolong decision-making prior to starting hormone therapy to help align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g. exercise) yet if and how tendon adaptation is influenced by sex and gender-affirming hormone therapy during growth remains unknown. The goal of this study was to understand how pubertal suppression followed by testosterone influences the structural and functional properties of the Achilles tendon using an established adolescent mouse model of testosterone hormone therapy.</p><p><strong>Materials and methods: </strong>C57BL/6N female mice were assigned at postnatal day 26 to the following experimental groups: control (vehicle treated), gonadotropin release hormone analogue (GnRHa) treatment alone to delay puberty, testosterone (T) alone after puberty, or delayed puberty with T treatment (i.e. GnRHa followed by T).</p><p><strong>Results: </strong>We found that pubertal suppression using GnRHa with and without T, as well as treatment with T alone post-puberty, increased the ultimate load of tendon in female mice. Additionally, we found that GnRHa, but not T treatment resulted in a significant increase in cell density at the Achilles enthesis.</p><p><strong>Conclusions: </strong>These findings demonstrate that delayed puberty and T have no negative influence on structural or functional properties of mouse tendon.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"96-106"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522759","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}
Caitlin M Hopkins, Benjamin T Wilks, Jeffrey R Morgan
{"title":"TGF-β1 requires IL-13 to sustain collagen accumulation and increasing tissue strength and stiffness.","authors":"Caitlin M Hopkins, Benjamin T Wilks, Jeffrey R Morgan","doi":"10.1080/03008207.2025.2469575","DOIUrl":"10.1080/03008207.2025.2469575","url":null,"abstract":"<p><strong>Aims: </strong>Fibrosis is a multifactorial process characterized by the excessive accumulation of extracellular matrix (ECM), increased tissue stiffness, and decreased elasticity. This study examined how individual cytokines and a cytokine combination alter collagen production and biomechanics in a 3D in vitro model of the human ECM.</p><p><strong>Methods: </strong>Cultured human fibroblasts were seeded into a circular agarose trough molded in 24 well plates. The fibroblasts aggregated and formed a 3D ring-shaped tissue that synthesized de novo a collagen-rich human ECM complete with collagen fibrils. Unlike existing models, no macromolecular crowders were added, nor artificial scaffolds or exogenous ECM proteins. Rings were treated with TGF-β1, IL-13 or the combination of TGF-β1 and IL-13 for up to 3 weeks. Morphology, histology, collagen, DNA, fibril formation, gene expression and tensile properties of the rings were measured.</p><p><strong>Results: </strong>As the rings compacted, cellularity and total DNA decreased, whereas total collagen accumulated. TGF-β1 stimulated collagen accumulation and increased ring biomechanics at day 7, but these increases stalled and declined by day 21. When treated with IL-13, a cytokine exclusive to the immune system, there were no significant differences from control. However, when TGF-β1 was combined with IL-13, collagen levels and ring biomechanics increased over the entire three weeks to levels higher than TGF-β1 alone. Gene expression was differentially regulated by cytokine treatment over the entire three weeks suggesting that increased collagen accumulation was not due to upregulation of collagen gene expression.</p><p><strong>Conclusions: </strong>These results suggest that TGF-β1 requires a second signal, such as IL-13, to sustain the long-term pathological increases in collagen accumulation and biomechanics that can compromise the function of fibrotic tissues.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"107-120"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514957","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}
Lin Liu, Zhuangzhuang Chu, Xiao Han, Jin Wu, Kunzhan Cai, Jiaohong Wang, Zixiang Guo, Shan Gao, Guoqing Li, Chunbo Tang
{"title":"Creatine promotes osteogenic differentiation of dental pulp stem cells via the AMPK-ULK1-autophagy axis.","authors":"Lin Liu, Zhuangzhuang Chu, Xiao Han, Jin Wu, Kunzhan Cai, Jiaohong Wang, Zixiang Guo, Shan Gao, Guoqing Li, Chunbo Tang","doi":"10.1080/03008207.2025.2459243","DOIUrl":"10.1080/03008207.2025.2459243","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.</p><p><strong>Materials and methods: </strong>HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.</p><p><strong>Results: </strong>We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.</p><p><strong>Conclusion: </strong>Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"73-86"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390233","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}
John M Lawler, Khaled Y Kamal, Rachel E Botchlett, Shih Lung Woo, Honggui Li, Jeff M Hord, James D Fluckey, Chaodong Wu
{"title":"Metformin ablates high fat diet-induced skeletal muscle hypertrophy and elevation of sarcolemmal GLUT4 when feeding is initiated in young adult male mice.","authors":"John M Lawler, Khaled Y Kamal, Rachel E Botchlett, Shih Lung Woo, Honggui Li, Jeff M Hord, James D Fluckey, Chaodong Wu","doi":"10.1080/03008207.2025.2471853","DOIUrl":"10.1080/03008207.2025.2471853","url":null,"abstract":"<p><p>A high-fat diet (HFD) and metabolic disease can impair insulin signaling in skeletal muscle, including a reduction in IRS-1 and GLUT-4 at the cell membrane. Other sarcolemmal proteins (e.g. caveolin-3, nNOS) within the dystrophin-glycoprotein complex (DGC) are partially lost with Type II diabetes. Thus, we hypothesized that a HFD would cause a significant loss of sarcolemmal DGC proteins and GLUT4, and the anti-diabetic drug metformin would mitigate the disruption of the DGC and preserve sarcolemmal GLUT4 on the soleus muscle. Eight-week-old mice were fed a high-fat diet for 12 weeks. After 8 weeks, one-half of the HFD mice received metformin for the remaining 4 weeks. HFD caused a marked increase in soleus muscle mass and fiber cross-sectional area and elevated sarcolemmal GLUT4, even though systemic insulin resistance was greater. HFD-induced muscle hypertrophy and elevated membrane GLUT4 were unexpectedly attenuated by metformin. In addition, IRS-1 positive staining was not reduced by HFD but rather enhanced in the metformin mice fed a high-fat diet. Sarcolemmal staining of dystrophin and caveolin-3 was reduced by HFD but not in the metformin group, while nNOS intensity was unaffected by HFD and metformin. These findings suggest that skeletal muscles in young adult mice can compensate for a high-fat diet and insulin resistance, with a minor disruption of the DGC, by maintaining cell membrane nNOS and IRS-1 and elevating GLUT4. We postulate that a window of compensatory GLUT4 and nNOS signaling allows calorically dense food to enhance skeletal muscle fiber size when introduced in adolescence.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"121-135"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572266","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}
Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang
{"title":"IGF2BP3 facilitates the osteogenic differentiation of bone marrow mesenchyml stem cells via upregulating KLK4.","authors":"Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang","doi":"10.1080/03008207.2025.2458129","DOIUrl":"10.1080/03008207.2025.2458129","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.</p><p><strong>Methods: </strong>RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.</p><p><strong>Results: </strong>KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.</p><p><strong>Conclusion: </strong>These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"49-58"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482127","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":"α-Ketoglutarate promotes autophagic activity under a peri-implant condition to enhance osseointegration of dental implant in rats with osteoporosis.","authors":"Luyuan Chen, Qisen Li, Shengnan Ma, Bohua Wang","doi":"10.1080/03008207.2024.2442675","DOIUrl":"10.1080/03008207.2024.2442675","url":null,"abstract":"<p><strong>Aim: </strong>We aimed to investigate whether α-ketoglutarate (AKG) can promote autophagic activity under a peri-implant condition to enhance the osseointegration of dental implant in rats with osteoporosis (OP).</p><p><strong>Methods: </strong>Con, Model and AKG groups were established for the random allocation of thirty rats (<i>n</i> = 10). Their bone metabolism indicators were measured. The peri-implant bone morphology was detected by toluidine blue staining, the peri-implant bone tissue healing was detected, and the implant torque was measured.</p><p><strong>Results: </strong>In comparison to the Con group, the bone metabolism indicators [bone volume/tissue volume ratio (BV/TV), trabecular number (Tb.N), and osseointegration index (OI)], bone-implant contact (BIC) rate, bone mass in the cancellous area, dislocation torque, protein and mRNA expressions of bone morphogenetic protein-2 (BMP-2), RUNX2 and Beclin1, and LC3II/LC3I ratio in bone tissues decreased significantly in the Model group, with a significant enlargement of trabecular space (Tb.Sp) (<i>p</i> < 0.05). In comparison with the Model group, the AKG group had significant increases in Tb.N, BV/TV, OI, BIC rate, bone mass in the cancellous area, dislocation torque, mRNA plus protein expressions of BMP-2, Runt-related transcription factor 2 and Beclin1, and LC3II/light chain 3I ratio in bone tissues, in addition to a significant reduction of Tb.Sp (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>AKG may relieve the bone metabolism disorders and enhance the osteogenic differentiation and osseointegration of implants in OP rats by promoting peri-implant autophagy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881633","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":"Assembly of collagen fibers into contiguous dense and loose regions of subcutaneous fascia.","authors":"Natsuki Maeda, Takafumi Watanabe, Daisuke Suzuki, Tomohito Iwasaki, Yongchol Shin, Yasutada Imamura","doi":"10.1080/03008207.2025.2455730","DOIUrl":"10.1080/03008207.2025.2455730","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the collagen fiber structure of the subcutaneous fascia, a connective tissue layer between the skin and epimysium.</p><p><strong>Methods: </strong>Fascia samples with varying extensibility were examined using biochemical and microscopic methods.</p><p><strong>Results: </strong>Loose fascia, the more extensible type, displayed sparsely distributed collagen fibers, while dense fascia showed tightly packed collagen fiber bundles. Elastase treatment, after urea pretreatment, caused the loosening of collagen fiber bundles and increased collagen fiber generation as the treatment time increased. This suggests that elastic fibers contribute to collagen fiber bundle formation. Additionally, elastase treatment stretched the fascia, indicating the presence of twodimensional tensile stress generated by elastic fibers. Either enzymes capable of cleaving elastic fibers may be activated or the stretching of elastic fibers accompanying tissue deformation may increase the enzyme sensitivity to elastic fibers, leading to the formation of localized collagen fibers in vivo. Tissue staining confirmed that loose and dense fascia corresponded to areas with sparse and dense collagen fibers, respectively. Some dense collagen fibers appeared to migrate and disperse into loose areas.</p><p><strong>Conclusion: </strong>These findings provide insights into the structural organization and functional significance of collagen fibers within the subcutaneous fascia. They particularly highlight the role of elastic fibers in maintaining tissue integrity and facilitating dynamic remodeling.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"26-36"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058375","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}
Lauren Paschall, Ariane Tsai, Erdem Tabdanov, Kara Negrini, Jenelle Izer, Aman Dhawan, Spencer E Szczesny
{"title":"Allograft and autograft anterior cruciate ligament reconstructions exhibit a similar biological response to cyclic loading.","authors":"Lauren Paschall, Ariane Tsai, Erdem Tabdanov, Kara Negrini, Jenelle Izer, Aman Dhawan, Spencer E Szczesny","doi":"10.1080/03008207.2025.2456957","DOIUrl":"10.1080/03008207.2025.2456957","url":null,"abstract":"<p><strong>Objective: </strong>Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. While outcomes are similar in the general patient population, the rerupture rate of non-irradiated allografts are 3-4 times higher than autografts in young active individuals. Previous studies suggest that the difference in clinical performance between graft types is due to impaired remodeling in allografts in response to loading. The objective of this study was to compare the remodeling response of autografts and allografts to cyclic loading. Furthermore, given that allografts are a foreign object and that immune cell signaling affects fibroblast mechanobiology, we compared markers of the immune cell composition between graft types.</p><p><strong>Methods: </strong>ACL reconstructions were performed on New Zealand white rabbits, harvested 8 weeks post-surgery, and cyclically loaded to 2 MPa in a tensile bioreactor. Expression of markers for anabolic and catabolic tissue remodeling, as well as inflammatory cytokines and immune cells, were quantified using quantitative reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>We found that the expression of markers for tissue remodeling were not different between allografts and autografts. Similarly, we found that the expression of markers for immune cells were not different between allografts and autografts.</p><p><strong>Conclusions: </strong>These data suggest that the poor clinical outcomes and impaired remodeling of allograft reconstructions compared to autografts is not due to a difference in graft mechanobiology.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"37-48"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481777","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}