Some anti-diabetic therapies can have adverse effects on bone health and increase fracture risk. In this study, we tested the skeletal effects of chronic administration of two Glucagon-like peptide-1 receptor agonists (GLP-1RA), increasingly used for type 2 diabetes treatment, in a model of osteoporosis associated bone loss and examined the expression and activation of GLP-1R in bone cells. Mice were ovariectomised (OVX) to induce bone loss and four weeks later they were treated with Liraglutide (LIR) 0.3mg/kg/day, Exenatide (Ex-4) 10 μg/kg/day or saline for four weeks. Mice were injected with calcein and alizarin red prior to euthanasia, to label bone-mineralising surfaces. Tibial micro-architecture was determined by micro-CT and bone formation and resorption parameters measured by histomorphometric analysis. Serum was collected to measure calcitonin and sclerostin levels, inhibitors of bone resorption and formation, respectively. GLP-1R mRNA and protein expression were evaluated in the bone, bone marrow and bone cells using RT-PCR and immunohistochemistry. Primary osteoclasts and osteoblasts were cultured to evaluate the effect of GLP-1RA on bone resorption and formation in vitro. GLP-1RA significantly increased trabecular bone mass, connectivity and structure parameters but had no effect on cortical bone. There was no effect of GLP-1RA on bone formation in vivo but an increase in osteoclast number and osteoclast surfaces was observed with Ex-4. GLP-1R was expressed in bone marrow cells, primary osteoclasts and osteoblasts and in late osteocytic cell line. Both Ex-4 and LIR stimulated osteoclastic differentiation in vitro but slightly reduced the area resorbed per osteoclast. They had no effect on bone nodule formation in vitro. Serum calcitonin levels were increased and sclerostin levels decreased by Ex-4 but not by LIR. Thus, GLP-1RA can have beneficial effects on bone and the expression of GLP-1R in bone cells may imply that these effects are exerted directly on the tissue.

Campylobacter species (spp.) are one of the most important causes of human bacterial gastroenteritis in foods of animal origin. Recently, with the spread of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Campylobacter spp., natural alternative therapeutic methods are urgently required. Phytogenic active principles have gained considerable attention due to their proficiency to enhance gut health and, thereby, performance of broiler chickens. Thus, the current study aims to determine the prevalence and antimicrobial resistance of Campylobacter spp. of different chicken sources in Sharkia Governorate, Egypt, and to assess the growth-promoting, immunostimulant and antimicrobial effects of a mixture of eugenol and trans-cinnamaldehyde in an in vivo approach. A total of 101 (67.3%) campylobacter isolates was identified, according to both phenotypic and genotypic techniques. Moreover, all of the campylobacter isolates were resistant to erythromycin, trimethoprim/sulfamethoxazole, and ampicillin (100% each). Of note, a dietary supplementation of the mixture of eugenol and trans-cinnamaldehyde led to a significant improvement of the feed conversion ratio and body weight gain and a decrease in the cecal C. jejuni loads in the broilers challenged with XDR C. jejuni. Additionally, eugenol and the trans-cinnamaldehyde mixture had protective activities via the down-regulation of XDR C. jejuni (flaA, virB11 and wlaN) virulence genes and proinflammatory cytokines (TNF-α, IL-2, IL-6, and IL-8), and the up-regulation of anti-inflammatory cytokine IL-10. Thus, we recommend the usage of a mixture of eugenol and trans-cinnamaldehyde as an alternative to antimicrobials for the control and treatment of campylobacter infections.

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n=8/group) were orally treated for 3months with either 100mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA.

Glucocorticoid-induced secondary osteoporosis is the most predictable side effect of this anti-inflammatory. One of the main mechanisms by which glucocorticoids achieve such deleterious outcome in bone is by antagonizing Wnt/β-catenin signaling. Sclerostin, encoded by Sost gene, is the main negative regulator of the proformative and antiresorptive role of the Wnt signaling pathway in the skeleton. It was hypothesized that the partial inactivation of sclerostin function by genetic manipulation will rescue the osteopenia induced by high endogenous glucocorticoid levels. Sost-deficient mice were crossed with an established mouse model of excess glucocorticoids, and the effects on bone mass and structure were evaluated. Sost haploinsufficiency did not rescue the low bone mass induced by high glucocorticoids. Intriguingly, the critical manifestation of Sost deficiency combined with glucocorticoid excess was sporadic, sudden, unprovoked, and nonconvulsive death. Detailed histopathologic analysis in a wide range of tissues identified peracute hemopericardium and cardiac tamponade to be the cause. These preclinical studies reveal outcomes with direct relevance to ongoing clinical trials that explore the use of antisclerostin antibodies as a treatment for osteoporosis. They particularly highlight a potential for increased cardiovascular risk and may inform improved stratification of patients who might otherwise benefit from antisclerostin antibody treatment.

Mice harbouring a dentin matrix protein 1 (Dmp1) promoter-driven human diphtheria toxin (DT) receptor (HDTR) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT) littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2), was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

Background: Camel pathology research has evolved significantly over the past five decades, reflecting the growing recognition of camels’ importance in agriculture, zoonotic disease control, and economic contributions. However, there has been limited evaluation of research trends, thematic advancements, and international collaborations in this field. Aim: This study aimed to conduct a bibliometric analysis of camel pathology research published between 1971 and 2024. Methods: The study identified key research themes, assessed collaboration patterns, and highlighted gaps to guide future research efforts in camel pathology. Results: The analysis included 297 research articles retrieved from Scopus. A steady increase in publications was observed, with a notable surge after 2010 due to advancements in molecular techniques and rising global interest in camel health. Thematic analysis identified well-established motor themes, such as camel histopathology and tuberculosis, while basic themes like infertility and postmortem studies were found to be underexplored. Collaboration analysis revealed the dominance of Saudi Arabia and Egypt, emphasizing their pivotal role in camel research. However, under-represented regions, such as Sub-Saharan Africa, showed limited participation in collaborative networks. Conclusion: This study highlights the transition from traditional pathological techniques to advanced molecular and epidemiological approaches, enabling better disease detection, diagnosis, and management in camels. Despite significant progress, the slower adoption of cutting-edge technologies in certain regions indicates the need for targeted capacity-building initiatives. By addressing these gaps and fostering international collaborations, camel pathology research can contribute to sustainable development, improved public health, and improved global food security.