Effects and Reversibility of Pre- and Post-natal Iron and Omega-3 Fatty Acid Deficiency, Alone and in Combination, on Bone Development in Rats

Both iron and omega-3 (n-3) polyunsaturated fatty acids may play an important role in bone development. The aim of this study was to investigate the effects of pre- and post-natal iron and n-3 fatty acid deficiency (FAD), alone and in combination, on bone development in rats, and to determine whether effects are reversible when a sufficient diet is provided post-weaning. Using a 2×2-factorial design, 56 female Wistar rats were allocated to one of four diets: (1) control, (2) iron deficient (ID), (3) n-3 FAD or (4) ID and n-3 FAD, and were maintained on the respective diets throughout gestation and lactation. At weaning (post-natal day [PND] 21), offspring (n = 24/group; male:female=1:1) were randomly allocated to either continue with their respective diets or to switch to the control diet until PND 42-45. Bone mineral density (BMD) and bone strength were determined using dual X-ray absorptiometry and three-point bending tests, respectively. Pre- and post-natal ID resulted in significantly lower BMD in the spine and bone strength in the left femur. Both ID and n-3 FAD resulted in lower BMD in the right femur, with an additive reduction in the combined ID and n-3 FAD group vs. controls. While negative effects of pre- and post-natal ID alone were reversed in offspring switched to a control diet post-weaning, lower BMD and bone strength persisted in offspring with combined ID and n-3 FAD during the prenatal and early post-natal period. Effects were not sex-specific. These results indicate that ID during early life may negatively influence bone development, with potential additive effects of n-3 FAD. While the effects of ID alone seem reversible, a combined ID and n-3 FAD may result in irreversible deficits in bone development.

Nutritional Approaches as a Treatment for Impaired Bone Growth and Quality following the Consumption of Ultra-Processed Food

The severe impairment of bone development and quality was recently described as a new target for unbalanced ultra-processed food (UPF). Here, we describe nutritional approaches to repair this skeletal impairment in rats: supplementation with micro-nutrients and a rescue approach and switching the UPF to balanced nutrition during the growth period. The positive effect of supplementation with multi-vitamins and minerals on bone growth and quality was followed by the formation of mineral deposits on the rats’ kidneys and modifications in the expression of genes involved in inflammation and vitamin-D metabolism, demonstrating the cost of supplementation. Short and prolonged rescue improved trabecular parameters but incompletely improved the cortical parameters and the mechanical performance of the femur. Cortical porosity and cartilaginous lesions in the growth-plate were still detected one week after rescue and were reduced to normal levels 3 weeks after rescue. These findings highlight bone as a target for the effect of UPF and emphasize the importance of a balanced diet, especially during growth.

Wnt Pathway Extracellular Components and Their Essential Roles in Bone Homeostasis

The Wnt pathway is involved in several processes essential for bone development and homeostasis. For proper functioning, the Wnt pathway is tightly regulated by numerous extracellular elements that act by both activating and inhibiting the pathway at different moments. This review aims to describe, summarize and update the findings regarding the extracellular modulators of the Wnt pathway, including co-receptors, ligands and inhibitors, in relation to bone homeostasis, with an emphasis on the animal models generated, the diseases associated with each gene and the bone processes in which each member is involved. The precise knowledge of all these elements will help us to identify possible targets that can be used as a therapeutic target for the treatment of bone diseases such as osteoporosis.

Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis. Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test. Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P< 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.

BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female Bmp3−/− mice. To investigate the effect of Bmp3 from birth to maturity, we compared Bmp3−/− mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age. Bmp3 deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The Bmp3 reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of Bmp3−/− mice. Bmp3 deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult Bmp3−/− mice.

Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis

Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.

Construction of developmentally inspired periosteum-like tissue for bone regeneration

The periosteum, a highly vascularized thin tissue, has excellent osteogenic and bone regenerative abilities. The generation of periosteum-mimicking tissue has become a novel strategy for bone defect repair and regeneration, especially in critical-sized bone defects caused by trauma and bone tumor resection. Here, we utilized a bone morphogenetic protein-2 (BMP-2)-loaded scaffold to create periosteum-like tissue (PT) in vivo, mimicking the mesenchymal condensation during native long bone development. We found that BMP-2-induced endochondral ossification plays an indispensable role in the construction of PTs. Moreover, we confirmed that BMP-2-induced PTs exhibit a similar architecture to the periosteum and harbor abundant functional periosteum-like tissue-derived cells (PTDCs), blood vessels, and osteochondral progenitor cells. Interestingly, we found that the addition of chondroitin sulfate (CS), an essential component of the extracellular matrix (ECM), could further increase the abundance and enhance the function of recruited PTDCs from the PTs and finally increase the regenerative capacity of the PTs in autologous transplantation assays, even in old mice. This novel biomimetic strategy for generating PT through in vivo endochondral ossification deserves further clinical translation.

Is bone kinesthetic adaptation of bone innervation plastically developed in fingers and correlated joints of violist and pianist after long term practice?

Bone cells might be considered in response to the distribution of nerves in the periosteum, epiphysis and bone marrow.The sensory and sympathetic neurotransmitters have trophic effects critically on normal osteogenic differentiation and bone metabolism in bone development and regeneration. It could modulate bone regeneration, bone remodeling, and articular cartilage homeostasis to their classic neurological actions. With touching and hearing mediated osseoperception, sensation can be adapted from the mechanical stimulation of a bone-anchored prosthesis. Investigations of the influence of music on the human brain showed structural and functional cerebro-neuroplasticity emerge as a result of long-term musical practice, which may cause cognitive differences between non-musicians and musicians. Meanwhile, the physical mechanical hits and touch strings and keys of instruments hypothetically were considered to cause adaptability for professional musicians in their peripheral tissues, especially bone sensation of fingers and correlated joints. Music practice is bone-strengthening activity. We hypothesis that it produces sensation adaptation in the fingers and correlated joints of instrument players, especially musicians after tremendous training and practice. Both the bone, correlated joint and its innervation are adapted by neuroplasticity for something part of “hardware constructing” to accomplish music performance. We thought that neuroplasticity occurred both in central nervous system and peripheral nervous system. Besides of developed in soft tissues of subcutaneous, connective tissue, muscle, inter-tissue coordination through neuro-network may occur in bone innervation coupled with correlated joint for specialized music-practice-oriented neuroplasticity. Soft tissues, such as muscle and tendon cannot directly hit instrument with stiffness to generate sound and rhythmic. Functionally, innervated-bone as bio-mechanical device becomes sensory musical target bone.

Effects of pen enrichment on leg health of fast and slower-growing broiler chickens

Pen enrichment for broiler chickens is one of the potential strategies to stimulate locomotion and consequently contribute to better leg health and welfare. This study was designed to evaluate effects of using a plethora of pen enrichments (barrier perches, angular ramps, horizontal platforms, large distance between feed and water and providing live Black Soldier fly larvae in a dustbathing area) on tibia characteristics, locomotion, leg health and home pen behaviour of fast and slower-growing broiler chickens. The experiment was set up as a 2 x 2 factorial arrangement with a total of 840 male broiler chickens in a complete randomized design (7 pens per treatment and 30 chickens per pen) with the following treatments: 1) pen enrichment (enriched pen or non-enriched pen); 2) broiler strain (fast-growing Ross 308 or slower-growing Hubbard JA 757). Home pen behaviour and use of enrichment were observed. At approximately 1400 and 2200 g body weight, two chickens per pen were randomly selected and slaughtered, to investigate tibia morphological, biophysical and mechanical characteristics and leg health. Pen enrichment positively affected tibia biophysical characteristics, e.g., osseous volume (Δ = 1.8 cm3, P = 0.003), total volume (Δ = 1.4 cm3, P = 0.03) and volume fraction (Δ = 0.02%, P = 0.002), in both fast and slower-growing chickens, suggesting that pen enrichment particularly affects ossification and mineralization mechanisms. Accordingly, locomotion and active behaviours were positively influenced by pen enrichment. However, pen enrichment resulted in lower body weight gain in both strains, which might be due to higher activity or lower feed intake as a result of difficulties of crossing the barrier perches. Regarding the strain, slower-growing chickens showed consistently more advanced tibia characteristics and more active behaviour than fast-growing chickens. It can be concluded that pen enrichment may lead to more activity and better bone development in both fast and slower-growing chickens.

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

Vasculature plays a key role in bone development and the maintenance of bone tissue throughout life. The two organ systems are not only linked in normal physiology, but also in pathophysiological conditions. The chronic kidney disease–mineral and bone disorder (CKD-MBD) is still the most serious complication to CKD, resulting in increased morbidity and mortality. Current treatment therapies aimed at the phosphate retention and parathyroid hormone disturbances fail to reduce the high cardiovascular mortality in CKD patients, underlining the importance of other factors in the complex syndrome. This review will focus on vascular disease and its interplay with bone disorders in CKD. It will present the very late data showing a direct effect of vascular calcification on bone metabolism, indicating a vascular-bone tissue crosstalk in CKD. The calcified vasculature not only suffers from the systemic effects of CKD but seems to be an active player in the CKD-MBD syndrome impairing bone metabolism and might be a novel target for treatment and prevention.