Bovine colostrum improves bone microstructure in ovariectomized and orchidectomy rats via VEGFA signaling

Abstract

Research has shown that components of bovine colostrum (BC), as lactoferrin, induce bone anabolic effects. However, the effects of BC supplementation as a whole in bone microarchitecture and the mechanisms through which BC may induce bone anabolic effects is relatively unclear. The aim of this study was to evaluate the effects of different BC doses supplementation in ovariectomized (OVX) and orchidectomy (ORX) rat-models and to identify the pathways that may mediate the action of BC on bone. Methods: After baseline measurements of bone microarchitecture (μCT), twenty-seven-month-old female (OVX, n=32) and male (ORX, n=32) Wistar rats were randomly assigned to the following groups: a) placebo b) BC dose 1 (0.5g/day/females; 1.0g/day/males), c) BC dose 2 (1g/day/females; 1.5g/day/males) and d) BC dose 3 (1.5g/day/females; 2g/day/males). After 4 months of supplementation, bone microarchitecture was re-assessed. Gene expression of VEGFA, FGF2, TATA, OPG, RANK and RANKL were measured by qRT-PCR. The study was approved by the National Ethics Committee for the Use of Animals in Research. Results: Regarding male rats, BC dose 1 significantly improved bone microarchitecture, as these rats not only revealed significantly less cortical porosity (41.9%, p<0.05) and cortical pore size (25.7%, p<0.05) compared to placebo group, but also significantly increased cortical volume (89.7%, p<0.05), cortical BMD (134.9%, p<0.01), trabecular thickness (37.3%, p<0.01), trabecular volume (24.6%, p<0.001) and trabecular BMD (7.5%, p<0.01). BC dose 2 induced the same effects as dose 1 for male rats, and significantly reduced trabecular porosity (8.1%, p<0.01), while dose 3 reduced trabecular separation (29.3%, p<0.05). As for female rats, BC dose 1 did not induce positive effects on bone microarchitecture. However, BC dose 2 and 3 decreased cortical porosity (placebo: 65.75+/-4.22; dose 2: 25.16+/-8.83; dose 3: 25.22+/-8.54%, p<0.01) and improved trabecular thickness (placebo: 12.22+/-0.99; dose 2: 21.11+/-3.28; dose 3: 18.39+/-2.45μm, p<0.01) compared to placebo. BC dose 3 significantly increased mRNA expression of VEGFA (2.37+/-1.83, p<0.05). Conclusion: BC preserves bone mass of OVX and ORX rats by stimulating bone formation. Indeed, as bone is a high vascularized organ and VEGFA plays important roles in vascular development and angiogenesis, it seems that VEGFA is influencing skeletal development and osteogenesis in OVX and ORX rats.