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Gain-of-function mutations in fibroblast growth factor receptor (FGFR) genes lead to chondrodysplasia and craniosynostoses. FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, we analyzed the impact of Fgfr2- and Fgfr3-activating mutations on mandibular bone formation and endochondral bone repair after non-stabilized mandibular fractures in mouse models of Crouzon syndrome (Crz) and hypochondroplasia (Hch). Bone mineralization of the calluses was abnormally high in Crz mice and abnormally low in Hch mice. The latter model presented pseudarthrosis and impaired chondrocyte differentiation. Spatial transcriptomic analyses of the Hch callus revealed abnormally low expression of Col11, Col1a, Dmp1 genes in mature chondrocytes. We found that the expression of genes involved in autophagy and apoptosis (Smad1, Comp, Birc2) was significantly perturbed and that the Dusp3, Dusp9, and Socs3 genes controlling the mitogen-activated protein kinase pathway were overexpressed. Lastly, we found that treatment with a tyrosine kinase inhibitor (BGJ398, infigratinib) or a C-type natriuretic peptide (BMN111, vosoritide) fully rescued the defective endochondral bone repair observed in Hch mice. Taken as a whole, our findings show that FGFR3 is a critical orchestrator of bone repair and provide a rationale for the development of potential treatments for patients with FGFR3-osteochondrodysplasia. [ABSTRACT FROM AUTHOR]

Background: It is accepted that the metabolic response of bone tissue depends on the intensity of the mechanical loads, but also on the type and frequency of stress applied to it. Physical exercise such as running involves stresses which, under certain conditions, have been shown to have the best osteogenic effects. However, at high intensity, it can be deleterious for bone tissue. Consequently, there is no clear consensus as to which running modality would have the best osteogenic effects. Aim: Our objective was to compare the effects of three running modalities on morphological and micro-architectural parameters on forelimb bones. Methods: Forty male Wistar rats were randomly divided into four groups: high intensity interval training (HIIT), continuous running, combined running ((alternating HIIT and continuous modalities) and sedentary (control). The morphometry, trabecular microarchitecture and cortical porosity of the ulna, radius and humerus were analyzed using micro-tomography. Results: All three running modalities resulted in bone adaptation, with an increase in the diaphyseal diameter of all three bones. The combined running protocol had positive effects on the trabecular thickness in the distal ulna. The HIIT protocol resulted in an increase in both medio-lateral diameter and cortical bone area over total area (Ct.Ar/Tt.Ar) at the ulnar shaft compared with sedentary condition. Moreover, the HIIT protocol decreased the mean surface area of the medulla (Ma.Ar) according to sedentary condition at the ulnar shaft. Conclusion: This study has shown that HIIT resulted in a decrease in trabecular bone fraction in favor of cortical bone area at the ulna. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate potential osteoarthritic alterations within the ankle using a surgically-induced chronic lateral ankle instability (CLAI) model. Twelve rats were assigned randomly to either the control (n = 4) or CLAI group (n = 8). Surgery was performed on the right ankle. Osteoarthritis was assessed through in-vivo micro-CT at 8 weeks and a clinical analysis. Macroscopic analysis, high-resolution ex-vivo micro-CT and histological examination were conducted after euthanasia at 12 weeks. Three subgroups (SG) were analyzed. SG1 comprised the operated ankles of the CLAI group (n = 8). SG2 consisted of the non-operated ankles of the CLAI group (n = 8). SG3 included both sides of the control group (n = 8). In-vivo micro-CT revealed no significant differences among the three subgroups when analyzed together (p = 0.42), and when comparing SG1 with SG2 (p = 0.23) and SG3 (p = 0.43) individually. No noticeable clinical differences were observed. After euthanasia, macroscopic analysis employing OARSI score, did not demonstrate significant differences, except between the medial tibia of SG1 and SG3 (p = 0.03), and in the total score comparison between these two subgroups (p = 0.015). Ex-vivo micro-CT did not reveal any differences between the three subgroups regarding bony irregularities and BV/TV measurements (SG1 vs. SG2 vs. SG3: p = 0.72; SG1 vs. SG2: p = 0.80; SG1 vs. SG3: p = 0.72). Finally, there was no difference between the three subgroups regarding OARSI histologic score (p = 0.27). These findings indicate that the current model failed to induce significant osteoarthritis. However, they lay the groundwork for improving the model's effectiveness and expanding its use in CLAI research, aiming to enhance understanding of this pathology and reduce unnecessary animal sacrifice. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by Wei and colleagues from Jilin University in China, which evaluated the use of stented aortic allografts (AA) for tracheal replacement in a rat model. The study found that the majority of the animals did not experience any postoperative complications and observed the regeneration of epithelium and cartilage within the aortic matrices from recipient cells. The authors of the article congratulate the authors of the study for confirming their own results and discuss the challenges of tracheal replacement and the various research approaches that have been explored. They also highlight the importance of understanding the mechanisms of tissue regeneration and immune responses in this process. [Extracted from the article]