Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Gut microbiota in regulation of childhood bone growth.

Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota-based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting.

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments.

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children's height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.

Dietary 25-hydroxy-cholecalciferol and additional vitamin E improve bone development and antioxidant capacity in high-density stocking broilers.

This study aimed to investigate the effects of diets supplemented with 25-hydroxycholecalciferol [25-(OH)D3] and additional vitamin E on growth performance, antioxidant capacity, bone development, and carcass characteristics at different stocking densities on commercial broiler farms. A total of 118,800 one-day-old Arbor Acres broilers were assigned to a 2 × 2 factorial treatment consisting of two dietary vitamin levels (5,500 IU vitamin D3 and 60 IU vitamin E: normal diet, using half 25-(OH)D3 as a source of vitamin D3 and an additional 60 IU of vitamin E: 25-(OH)D3+VE diet) and two stocking densities (high density of 20 chickens/m2: HD and 16 chickens/m2: LD). The experiment lasted for 42 d. The results showed that high-density stocking negatively affected the growth performance of broilers during the first four weeks, whereas the vitamin diet treatment significantly improved the feed conversion ratios (FCR) during the last 2 wk. Vitamin diets increased catalase at 14 and 42 d, and the glutathione peroxidase (GSH-px) levels at 42 d in high-density-stocked broilers. The interaction showed that serum vitamin E levels were significantly improved at 28 d of age in high-density-stocked broilers as a result of the vitamin diets. Stocking density and dietary treatments were found to significantly affect bone development, with the vitamin diet significantly increasing metatarsal length and femoral bone strength in broilers from high-density stocking density at 28 d of age. High stocking density increased the proportion of leg muscles and meat yield per square meter. In general, 25-(OH)D3 and additional vitamin E suppressed oxidative stress and ameliorated the negative effects of high-density stocking on bone development in a commercial chicken farm setting. Vitamin diets improved the FCR of broilers, while high-density stocking resulted in better economic outcomes.

High-density stocking is often associated with animal welfare risks in broilers, mainly in terms of oxidative stress and bone development. Nevertheless, farming at too low a density remains for the most part economically unviable. Modulation of antioxidant capacity and bone development by nutritional strategies in high-density-farmed broilers has proven an effective tool in developing countries. Therefore, the present study investigated the effects of applying diets with a higher biological potency of vitamin D3 25-hydroxycholecalciferol [25-(OH)D3] and a higher concentration of vitamin E on broiler production performance, antioxidant capacity and meat production performance at different densities of stocking under commercial farming conditions. The results indicated that the vitamin dietary treatments suppressed oxidative stress and ameliorated the negative effects of high-density farming on bone development.

Hydrolyzed Collagen Tripeptide Promotes Longitudinal Bone Growth in Childhood Rats via Increases in Insulin-Like Growth Factor-1 and Bone Morphogenetic Proteins.

Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 µg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01).

Effects of methylphenidate on femoral bone growth in male rats.

The use of Methylphenidate (MP) can have adverse effects on bone growth and mineralization. This study aimed to investigate the underlying pathophysiology of MP-induced skeletal deficits in growing rats using stereological and immunohistochemical methods. Male rats, aged 4 weeks, were orally treated with MP through an 8-h/day water drinking protocol. The rats (n=30) were randomly divided into three groups: MP-High Dose (30/60 mg/kg/day MP), MP-Low Dose (4/10 mg/kg/day MP), and control (water only). After 13 weeks, the femoral bones were assessed using calliper measurements, dual-energy X-ray absorptiometry, and biomechanical evaluation. The total femur volume, cartilage volume, growth zone volume, and volume fractions were determined using the Cavalieri method. Immunohistochemical analyses were conducted using alkaline phosphatase and anti-calpain antibody staining. Rats exposed to MP exhibited significant reductions in weight gain, femoral growth, bone mineralization, and biomechanical integrity compared to the control group. The total femoral volume of MP-treated rats was significantly lower than that of the control group. The MP-High Dose group showed significantly higher ratios of total cartilage volume/total femoral volume and total growth zone volume/total femoral volume than the other groups. Immunohistochemical evaluation of the growth plate revealed reduced osteoblastic activity and decreased intracellular calcium deposition with chronic MP exposure. The possible mechanism of MP-induced skeletal growth retardation may involve the inhibition of intracellular calcium deposition in chondrocytes of the hypertrophic zone in the growth plate. In this way, MP may hinder the differentiation of cartilage tissue from bone tissue, resulting in reduced bone growth and mineralization.

Perspective: A multi-trait integrative approach to understanding the structural basis of bone fragility for pediatric conditions associated with abnormal bone development.

Bone development is a highly orchestrated process that establishes the structural basis of bone strength during growth and functionality across the lifespan. This developmental process is generally robust in establishing mechanical function, being adaptable to many genetic and environmental factors. However, not all factors can be fully accommodated, leading to abnormal bone development and lower bone strength. This can give rise to early-onset bone fragility that negatively impacts bone strength across the lifespan. Current guidelines for assessing bone strength include measuring bone mineral density, but this does not capture the structural details responsible for whole bone strength in abnormally developing bones that would be needed to inform clinicians on how and when to treat to improve bone strength. The clinical consequence of not operationalizing how altered bone development informs decision making includes under-detection and missed opportunities for early intervention, as well as a false positive diagnosis of fragility with possible resultant clinical actions that may actually harm the growing skeleton. In this Perspective, we emphasize the need for a multi-trait, integrative approach to better understand the structural basis of bone growth for pediatric conditions with abnormal bone development. We provide evidence to showcase how this approach might reveal multiple, unique ways in which bone fragility develops across and within an array of pediatric conditions that are associated with abnormal bone development. This Perspective advocates for the development of new translational research aimed at informing better ways to optimize bone growth, prevent fragility fractures, and monitor and treat bone fragility based on the child's skeletal needs.

Indirubin-3'-oxime promotes the efficacy of GnRHa in obese-induced central precocious puberty and maintains normal bone growth and body weight via the ERK-Sp1-KISS-1/GPR54 axis.

Central precocious puberty (CPP) is a widespread developmental abnormality. The application of gonadotrophin-releasing hormone agonist (GnRHa) is widely useful for the medical therapy of CPP. This study aimed to investigate the combination effect and mechanism of indirubin-3'-oxime (I3O), an active ingredient analogue of traditional Chinese medicine, and GnRHa treatment on the progression of CPP. First, female C57BL/6 mice were fed with a high-fat diet (HFD) for the induction of precocious puberty and treated with GnRHa and I3O alone or in combination. Development of sexual maturation, bone growth and obesity were determined by vaginal opening detection, H&E staining and ELISA. The protein and mRNA expression levels of related genes were evaluated via western blotting, immunohistochemical method and RT-qPCR. Subsequently, tBHQ, an inhibitor of ERK, was applied to verify whether the mechanism of I3O was associated with this signaling. The results showed that the treatment of I3O alone or in combination with GnRHa could alleviate the HFD-induced earlier vaginal opening and serum levels of the gonadal hormone in mice. And, I3O could significantly eliminate the role of growth deceleration of GnRHa in bone development and reversed the side effect of GnRHa on body weight. More importantly, we found that I3O decreased the expression of KISS-1 and GPR54 by suppressing the phosphorylation of ERK1/2 and Sp1 in the hypothalamus in mice. In summary, these data indicated that I3O could promote the efficacy of GnRHa in HFD-induced precocious puberty, and maintain bone growth and body weight in mice via the ERK-Sp1-KISS-1/GPR54 axis.

Efficacy of dietary vitamin D3 and 25(OH)D3 on reproductive capacities, growth performance, immunity and bone development in pigs.

Vitamin D3 (Vit D3) and 25(OH)D3 are used as dietary sources of active vitamin D (1,25(OH)2D3) in pig husbandry. Although acting primarily on intestine, kidney and bone, their use in pig nutrition has shown a wide range of effects also in peripheral tissues. However, there is an ambiguity in the existing literature about whether the effects of Vit D3 and 25(OH)D3 differ in attributing the molecular and phenotypic outcomes in pigs. We searched Web of Science and PubMed databases concerning the efficacy of Vit D3 in comparison with 25(OH)D3 on pig physiology, i.e. reproductive capacities, growth performance, immunity and bone development. Dietary intake of Vit D3 or 25(OH)D3 did not influence the reproductive capacity of sows. Unlike Vit D3, the maternal intake of 25(OH)D3 significantly improved the growth performance of piglets, which might be attributed to maternally induced micronutrient efficiency. Consequently, even in the absence of maternal vitamin D supplementation, 25(OH)D3-fed offspring also demonstrated better growth than the offspring received Vit D3. Moreover, a similar superior impact of 25(OH)D3 was seen with respect to serum markers of innate and humoral immunity. Last but not least, supplements containing 25(OH)D3 were found to be more effective than Vit D3 to improve bone mineralisation and formation, especially in pigs receiving basal diets low in Ca and phosphorus. The insights are of particular value in determining the principal dietary source of vitamin D to achieve its optimum utilisation efficiency, nutritional benefits and therapeutic potency and to further improve animal welfare across different management types.

Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets.

Bone health problems are a serious threat to laying hens; microbiome-based therapies, which are harmless and inexpensive, may be an effective solution for bone health problems. Here, we examined the impacts of supplementation with Clostridium butyricum (CB) on bone and immune homeostasis in pullets. The results of in vivo experiments showed that feeding the pullets CB was beneficial to the development of the tibia and upregulated the levels of the bone formation marker alkaline phosphatase and the marker gene runt-related transcription factor 2 (RUNX2). For the immune system, CB treatment significantly upregulated IL-10 expression and significantly increased the proportion of T regulatory (Treg) cells in the spleen and peripheral blood lymphocytes. In the in vitro test, adding CB culture supernatant or butyrate to the osteoblast culture system showed no significant effects on osteoblast bone formation, while adding lymphocyte culture supernatant significantly promoted bone formation. In addition, culture supernatants supplemented with treated lymphocytes (pretreated with CB culture supernatants) stimulated higher levels of bone formation. In sum, the addition of CB improved bone health by modulating cytokine expression and the ratio of Treg cells in the immune systems of layer pullets. Additionally, in vitro CB could promote the bone formation of laying hen osteoblasts through the mediation of lymphocytes.

Effect of light intensity on growth performance and bone development of tibia in broilers.

Light management affects the health outcomes and growth performance of broiler chickens. However, the effects of different light intensities on growth performance and its association with tibia development of broilers remain unclear. In the present study, 462 Ross male broilers were divided into seven treatment groups with 6 replicates (11 birds per replicate), and then were subjected to different light intensity levels (0.5, 2, 5, 7, 9, 13 or 19 Lx) for 42 days. The results demonstrated that broilers under lower light intensity (2, 5Lx) obtained higher body weight (p < 0.05) and feed conversion ratio (p < 0.05). Lower light intensity exposure had no effects on the length, width, weight, breaking strength and the mineral density of the tibia (p > 0.05), but led to increased ash content and phosphorus during the starter phase (p < 0.05). Also, plasma levels of calcium (Ca), phosphorus (P) and alkaline phosphatase were increased in response to lower light intensity conditions (p < 0.05), but decreased under higher light intensity (p < 0.05), indicating dynamic mineral metabolic and depositional activity to light intensity. In addition, broilers exposed to lower intensity (0.5 Lx, 2 Lx and 5 Lx) during the starter phase had decreased hypertrophic chondrocytes (p < 0.05), but did not affect resting zone chondrocytes and proliferative chondrocytes of the growth plate (p > 0.05). In contrast, the light intensity did not affect the growth performance and the development of the tibia of broilers during the finishing phase. In summary, we demonstrated that lower light intensity promoted the growth performance and the bone development of broilers. Application of lower light intensity at the starter phase might be a management strategy for broiler industries.

Desordens hiperostóticas em American Bully / Hiperostotic disorders in american bully

O complexo de desordens hiperostóticas é uma condição rara e autolimitante, que tem as mesmas características histopatológicas, que cursa com proliferação óssea de caráter não neoplásico. Acomete cães jovens de raças distintas, com variabilidade quanto ao tipo de proliferação óssea e quanto aos ossos acometidos. O complexo é composto pela osteopatia craniomandibular, hiperostose da calota craniana e osteodistrofia hipertrófica. Podendo estar presente nos ossos da calota craniana, mandíbulas, coluna cervical e esqueleto apendicular. O presente relato, descreveu o quadro de uma cadela, da raça American Bully, não castrada, três meses de idade, que foi atendida com queixa de aumento de volume doloroso das mandíbulas, hiporexia e sialorreia há 15 dias, apresentando ao exame físico, amplitude de movimento diminuída e sensibilidade dolorosa da articulação temporomandibular, espessamento firme bilateral do crânio em região de fossa temporal, espessamento palpável de consistência firme das mandíbulas e crepitação respiratória. Após avaliação clínica e realização de exames complementares, chegou-se ao diagnóstico presuntivo, de complexo de desordens hiperostóticas. Foi instituído como conduta terapêutica o suporte analgésico, sendo eficaz para a manutenção das necessidades fisiológicas até a paciente alcançar a fase adulta. O prognóstico para esta paciente foi considerado bom, uma vez que não havia indícios de anquilose da articulação temporomandibular e/ou manifestações neurológicas.

The complex of hyperostotic disorders is a rare and self-limiting condition, which has the same histophatological characteristics, which courses with non-neoplastic bone proliferations. It affects young dogs of different breeds, with variability the bones affected. The complex is composed of craniomandibular osteopathy, calvarial hyperostotic syndrome and hypertrophic osteodystrophy. It may be present in the bones of the skullcap, jaws, cervical spine and appendicular skeleton. The present report describes the condition of a female dog, American Bully breed, entire, three months old, with a complaint of painful swelling of the jaws, hyporexia and drooling for 15 days, presenting on physical examination, reduced amplitude and pain of the temporomandibular joint, bilateral firm thickening of the skull in the temporal fossa region, palpable firm-consistent thickening of the mandibles and respiratory crackle. After clinical evaluation and complementary tests, a presumptive diagnosis of hyperostotic disorders complex was reached. It was instituted pain management as a treatment, being effective for the maintenance of physiological needs until the patient reaches the adulthood. The prognosis for this patient was considered good, since there was no evidence of temporomandibular joint ankylosis and/or neurological manifestations.

Comparing the potential of Bacillus amyloliquefaciens CGMCC18230 with antimicrobial growth promoters for growth performance, bone development, expression of phosphorus transporters, and excreta microbiome in broiler chickens.

Bone health of broiler chickens is essential for welfare and production. In this study, the probiotic Bacillus amyloliquefaciens (BA) CGMCC18230 was compared with antimicrobial growth promoters (AGPs) for its ability to promote growth and bone health. To address this, a total of 180 Arbor Acres (AA) 1-day-old, male, broiler chicks were randomly allocated into 3 treatment groups, with 6 replicates, containing 10 chicks in each replicate. The treatment groups were: control group (CON) fed a corn-soybean based diet; BA treatment group fed the basal diet supplemented with 2.5 × 1010 CFU/kg BA CGMCC18230; AGPs treatment group was fed the basal diet containing the antibiotics aureomycin (75 mg/kg), flavomycin (5 mg/kg) and kitasamycin (20 mg/kg). Over the 42 d experiment, broilers fed BA and AGPs diets both had higher BW, and the ADG was significantly (P < 0.05) higher than that of the CON group both in the grower phase (22-42 d) and overall. Moreover, with BA birds had higher (P < 0.05) serum concentrations of phosphorus (P, day 42) and alkaline phosphatase (ALP, days 21 and 42). Conversely, the content of P in excreta decreased significantly (P < 0.05) on days 21 and 42. Tibia bone mineralization was improved in BA, and the mRNA of P transport related genes PiT-1,2 in the duodenum and jejunum were significantly up-regulated in the BA group than in the CON group (P < 0.05). 16S rRNA gene sequencing revealed that dietary BA supplementation increased the relative abundance of butyrate-producing bacteria (Ruminococcaceae) and polyamine-producing bacteria (Akkermansia and Alistipes), which had a positive effect on bone development. These data show that dietary supplementation of BA CGMCC18320 improves broiler growth performance and bone health similar to supplementation with AGPs through up-regulation of intestinal P transporters, microbial modulation and increase P retention. However, no significant influence of BA CGMCC18320 supplementation on the retention of Ca was found.

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

OBJECTIVE: This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. METHODS: In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. RESULTS: According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. SIGNIFICANCE: It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants.

Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 µg/d (group-10) or 30 µg/d (group-30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2-year follow-up (p = 0.041) but not with bone (p = 0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] -0.50 [-0.98, -0.01] SD unit, p = 0.044) but not in the group-10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Novel peptides from sea cucumber intestinal hydrolysates promote longitudinal bone growth in adolescent mice through accelerating cell cycle progress by regulating glutamine metabolism.

Sea cucumber intestines are recognized as a major by-product in the sea cucumber processing industry and have been shown to exhibit bioactive properties. However, whether the sea cucumber intestine is beneficial for osteogenesis remains unknown. In this study, low molecular weight peptides rich in glutamate/glutamine were obtained from sea cucumber intestines (SCIP) by enzymatic hydrolysis, and orally administered to adolescent mice to investigate the effects on longitudinal bone growth. The results showed that the SCIP supplement significantly increased the femur length and new bone formation rate by 9.6% and 56.3%, and elevated the levels of serum osteogenic markers alkaline phosphatase (ALP), Collagen I and osteocalcin (OCN). Notably, H&E staining showed that SCIP significantly increased the height of the growth plate, in which the height of the proliferation zone was elevated by 95.6%. Glutamine is a major determinant of bone growth. SCIP supplement significantly increased glutamine levels in the growth plate by 44.2% and upregulated the expression of glutamine metabolism-related enzymes glutaminase 1 (Gls1) and glutamate dehydrogenase 1 (GLUD1) in the growth plate. Furthermore, SCIP supplement upregulated growth plate acetyl coenzyme A levels to promote histone acetylation and accelerated cell cycle progression by upregulating Sox9 expression, thereby contributing to rapid chondrocyte proliferation. To the best of our knowledge, this is the first report where SCIP could enhance longitudinal bone growth via promoting growth plate chondrocyte proliferation. The present study will provide new ideas and a theoretical basis for the high-value utilization of sea cucumber intestines.

The effect of intestinal flora intervention on bone development in children: A systematic review and meta-analysis.

BACKGROUND: The intestinal flora is involved in the bone development of children through a variety of mechanisms, but it remains unclear whether intervention of the intestinal flora can enhance children's bone development. METHODS: Six databases (PubMed, Web of Science, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health, and China National Knowledge Infrastructure) were searched for all English and Chinese studies published up to August 2021. Stata version 16.0 (StataCorp, College Station, TX, USA) was used. Bone mass density and biochemical markers related to bone metabolism were reported as the primary outcome, and the secondary outcomes were anthropometric parameters such as height, height Z score for age, and height velocity. Intergroup differences were determined by standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: A total of 3245 participants from 20 RCTs and 370 participants from 8 crossover trials were included in the study. Significant differences were found in bone mineral density (SMD 0.47; 95% CI, 0.28 to 0.66; p < 0.001; I2 = 0.00%) and total serum calcium (SMD 1.07; 95% CI, 0.39 to 1.74; p < 0.001; I2 = 61.9%), as well as in height Z score for age (SMD = 0.11; 95% CI, 0.00 to 0.22; P = 0.044; I2 = 0%). The overall quality of evidence ranged from moderate to very low. CONCLUSIONS: This systematic review and meta-analysis suggested that intestinal flora intervention was an effective method of improving bone mineral density, serum calcium, and height in infants, children, and adolescents. Future studies with a larger sample size and longer intervention period are needed. The protocol of this systematic review was registered in PROSPERO and the registered number was CRD42021282606.

Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats.

OBJECTIVE: The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats. METHODS: A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on. RESULTS: Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3. CONCLUSIONS: High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

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.