Cohort profile of an early life observational cohort in China: Bone and MicroBiOme onset (BAMBOO) study.

PURPOSE: The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. PARTICIPANTS: The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. FINDINGS TO DATE: The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. FUTURE PLANS: Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process. TRIAL REGISTRATION NUMBER: ChiCTR2100049972.

Resistance training presents beneficial effects on bone development of adolescents engaged in swimming but not in impact sports: ABCD Growth Study.

BACKGROUND: Sports practice during adolescence is important to enhance bone development, although it may provide different effects depending on the mechanical impact present in the sport. Besides, resistance training (RT) may also induce bone changes directly (via muscle contractions) and indirectly (via myokines). However, there have been no studies analyzing the longitudinal influence of engaging in sport with and without added mechanical load. Thus, this study aims to analyze the combined effects of sports participation and resistance training on areal bone mineral density (aBMD) accrual in adolescent athletes participating in swimming and impact sports for 12-months. METHODS: This was a 12-month longitudinal study. The sample comprised 91 adolescents (21 females) aged 10 to 18 years, engaged in impact sports (basketball, tennis, track & field, baseball and gymnastics, n = 66) and non-impact sport (swimming, n = 25). The sample was divided according to resistance training participation: impact sports only (n = 45), impact sports + resistance training (n = 21), swimming-only (n = 17) and swimming + resistance training (n = 8). aBMD and soft tissues were measured using dual-energy X-ray absorptiometry. Generalized linear models analysis was used for the resistance training (RT) x type of sport interaction in predicting aBMD changes overtime, adjusting for maturation, sex and baseline aBMD. RESULTS: After 12-months, all groups showed a significant increase in aBMD, except for the swimming groups (regardless of resistant training), which showed a significant loss in spine aBMD (-0.045 [-0.085 to -0.004] g/cm2 in swimming-only and - 0.047 [-0.073 to -0.021] g/cm2 in swimming + RT). In comparisons between groups, only swimming + RT group, compared with swimming-only group presented higher upper limbs aBMD (0.096 g/cm2 [0.074 to 0.118] in swimming + RT vs. 0.046 [0.032 to 0.060] g/cm2 in swimming only; p < 0.05) and whole body less head (WBLH) aBMD (0.039 [0.024 to 0.054] g/cm2 in swimming + RT vs. 0.017 [0.007 to 0.027] g/cm2 swimming-only; p < 0.05). CONCLUSION: Despite the significant gain in aBMD in all groups and body sites after 12-months, except for the spine site of swimmers, the results indicate that participation in RT seems to improve aBMD accrual in swimmers at the upper limbs and WBLH.

[Latest Findings on the Role of RUNX1 in Bone Development and Disorders]. / RUNX1åœ¨éª¨å‘è‚²åŠéª¨ç›¸å ³ç–¾ç— ä¸­çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.

Effect of Low Protein Diet on Bone Structure of Young Wistar Mice.

<b>Background and Objective:</b> Malnutrition and stunting are major unresolved problems in Indonesia. Protein deficiency can cause stunted growth, as well as make physical and cognitive abilities cannot reach their maximum potential. During childhood the need for protein must be fulfilled so that the peak of bone formation during adolescence can be perfect. In malnourished children, a low protein diet will lead to thinning of the bone cortex. Due to the high rate of stunting and malnutrition in children due to protein deficiency, a study was conducted on the effects of feeding low protein diet on rat bones. <b>Materials and Methods:</b> Male Wistar rats (n = 10) at 6-8 weeks old (body weight around 250 g), control groups were fed a normal chow diet and low protein diet groups were given low protein chow diet (protein 5%) for 18 weeks, then the rats were sacrificed and the femoral bones were isolated. Body weight, femur weight, femur length were checked and bone density was examined using X-ray. <b>Results:</b> The body proportions of the low protein group rats were smaller and thinner than those of the control group. This difference is supported by the significant weight loss starting from the sixth week after low protein feeding. There are significant differences in body weight and femur weight between the control and low protein diet groups. Bone density decreases significantly in low protein diet group. Macroscopically, the femur length of the low protein group was shorter than the control group, however the femur length did not show significant differences statistically between the two groups. <b>Conclusion:</b> A low protein diet decreased the body weight of the rats, also causing impaired bone growth characterized by decreasing femur weight. The low protein diet also caused osteoporosis in the bones.

Noncoding RNAs in skeletal development and disorders.

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.

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.

Does Microwave Exposure at Different Doses in the Pre/Postnatal Period Affect Growing Rat Bone Development?

Effects of pre/postnatal 2.45 GHz continuous wave (CW), Wireless-Fidelity (Wi-Fi) Microwave (MW) irradiation on bone have yet to be well defined. The present study used biochemical and histological methods to investigate effects on bone formation and resorption in the serum and the tibia bone tissues of growing rats exposed to MW irradiation during the pre/postnatal period. Six groups were created: one control group and five experimental groups subjected to low-level different electromagnetic fields (EMF) of growing male rats born from pregnant rats. During the experiment, the bodies of all five groups were exposed to 2.45 GHz CW-MW for one hour/day. EMF exposure started after fertilization in the experimental group. When the growing male rats were 45 days old in the postnatal period, the control and five experimental groups' growing male and maternal rats were sacrificed, and their tibia tissues were removed. Maternal rats were not included in the study. No differences were observed between the control and five experimental groups in Receptor Activator Nuclear factor-kB (RANK) biochemical results. In contrast, there was a statistically significant increase in soluble Receptor Activator of Nuclear factor-kB Ligand (sRANKL) and Osteoprotegerin (OPG) for 10 V/m and 15 V/m EMF values. Histologically, changes in the same groups supported biochemical results. These results indicate that pre/postnatal exposure to 2.45 GHz EMF at 10 and 15 V/m potentially affects bone development.

Stimulation of skeletal stem cells in the growth plate promotes linear bone growth.

Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epiphyseal skeletal stem cells, epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog (Hh) signaling. Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched1 (Ptch1) ablation in Pthrp-creER Ptch1fl/fl tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center of 1 leg of rats, this leg was significantly longer 1 month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced 2 and 6 months after implantation. We conclude that Hh signaling activates growth plate epSSCs, which effectively leads to increased longitudinal growth of bones. This opens therapeutic possibilities for the treatment of differences in leg length.

Gender-affirming hormone therapy preserves skeletal maturation in young mice via the gut microbiome.

Gender-affirming hormone therapy (GAHT) is often prescribed to transgender (TG) adolescents to alleviate gender dysphoria, but the effect of GAHT on the growing skeleton is unclear. We found GAHT to improve trabecular bone structure via increased bone formation in young male mice and not to affect trabecular structure in female mice. GAHT modified gut microbiome composition in both male and female mice. However, fecal microbiota transfers (FMTs) revealed that GAHT-shaped gut microbiome was a communicable regulator of bone structure and turnover in male, but not in female mice. Mediation analysis identified 2 species of Bacteroides as significant contributors to the skeletal effects of GAHT in male mice, with Bacteroides supplementation phenocopying the effects of GAHT on bone. Bacteroides have the capacity to expand Treg populations in the gut. Accordingly, GAHT expanded intestinal Tregs and stimulated their migration to the bone marrow (BM) in male but not in female mice. Attesting to the functional relevance of Tregs, pharmacological blockade of Treg expansion prevented GAHT-induced bone anabolism. In summary, in male mice GAHT stimulated bone formation and improved trabecular structure by promoting Treg expansion via a microbiome-mediated effect, while in female mice, GAHT neither improved nor impaired trabecular structure.

Knocking out FAM20C in pre-osteoblasts leads to up-regulation of osteoclast differentiation to affect long bone development.

Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1-10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein ß-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.

Chondrocyte hypertrophy in the growth plate promotes stress anisotropy affecting long bone development through chondrocyte column formation.

The length of long bones is determined by column formation of proliferative chondrocytes and subsequent chondrocyte hypertrophy in the growth plate during bone development. Despite the importance of mechanical loading in long bone development, the mechanical conditions of the cells within the growth plate, such as the stress field, remain unclear owing to the difficulty in investigating spatiotemporal changes within dynamically growing tissues. In this study, the mechanisms of longitudinal bone growth were investigated from a mechanical perspective through column formation of proliferative chondrocytes within the growth plate before secondary ossification center formation using continuum-based particle models (CbPMs). A one-factor model, which simply describes essential aspects of a biological signaling cascade regulating cell activities within the growth plate, was developed and incorporated into CbPM. Subsequently, the developmental process and maintenance of the growth plate structure and resulting bone morphogenesis were simulated. Thus, stress anisotropy in the proliferative zone that affects bone elongation through chondrocyte column formation was identified and found to be promoted by chondrocyte hypertrophy. These results provide further insights into the mechanical regulation of multicellular dynamics during bone development.

Combined toxicity of trifloxystrobin and fluopyram to zebrafish embryos and the effect on bone development.

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed. The results indicated that 96h-LC50 of TRI was 0.159 mg·L-1 to zebrafish embryo, which was highly toxic. The 96h-LC50 of FLU to zebrafish embryos was 4.375 mg·L-1, being moderately toxic. The joint toxicity to zebrafish embryos(FLU at 96h-LC50 and TRI at 96h-LC50 in a 1:1 weight ratio to form a series of concentration treatment groups) was antagonistic. Both trifloxystrobin and fluopyram also inhibited the skeletal development of zebrafish and showed to be antagonistic. The results of qPCR indicated upregulations of different genes upon three different treatments. TRI mainly induced Smads up-expression, which may affect the BMP-smads pathway. FLU mainly induced an up-expression of extracellular BMP ligands and type I receptor (Bmpr-1a), which may affect the BMP ligand receptor pathway. The 1:1 mixture (weight ratio) of trifloxystrobin and fluopyram induced a reduction of the genes of extracellular BMP ligand (Smads) and type I receptor (Bmpr1ba), which may down-regulate BMP signaling and thus attenuating cartilage hyperproliferation, hypertrophy and mineralization. The results warren an interest in further studying the effect of the two fungicides in a mixture on zebrafish.

Bone mass accrual in children.

PURPOSE OF REVIEW: Bone accrual during childhood and adolescence is critical for the attainment of peak bone mass and is a major contributing factor towards osteoporosis in later life. Bone mass accrual is influenced by nonmodifiable factors, such as genetics, sex, race, ethnicity, and puberty, as well as modifiable factors, such as physical activity and diet. Recent progress in bone imaging has allowed clinicians and researchers to better measure the morphology, density, and strength of the growing skeleton, thereby encompassing key characteristics of peak bone strength. In this review, the patterning of bone accrual and contributors to these changes will be described, as well as new techniques assessing bone mass and strength in pediatric research and clinical settings. RECENT FINDINGS: This review discusses factors influencing peak bone mass attainment and techniques used to assess the human skeleton. SUMMARY: The rate of bone accrual and the magnitude of peak bone mass attainment occurs in specific patterns varying by sex, race, ethnicity, longitudinal growth, and body composition. Physical activity, diet, and nutritional status impact these processes. There is a need for longitudinal studies utilizing novel imaging modalities to unveil factors involved in the attainment and maintenance of peak bone strength.

Effects of pseudoephedrine on rat fetal bone development: evaluation by three different methods.

Pseudoephedrine (PSE) is an agent that is contained in common cold medications. The agent, which is used to treat cold and cough, is the fourth most prescribed drug group in some countries. During pregnancy, expectant mothers use PSE for colds and other reasons. One out of every four expectant mothers use PSE alone or in combination with other medicines for various reasons. This study was aimed to investigate effects of PSE on long bones development in rat during fetal growth. Pregnant rats were divided into five groups: control and four experimental groups (25 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg PSE). Between 1 and 20 days of pregnancy, PSE was given to them by gavage. Weights and heights of fetuses isolated by cesarean on the 21st day were measured. Ossification of femur and humerus was examined by three different methods mentioned earlier. Depending on the dose increase, all morphometric data, ossification rate and bone length of the fetuses were decreased. Besides, it was determined that the amount of Calcium in the bone tissue decreased in the analyzes made with SEM-EDX Analysis. The data obtained from this study reveal that the use of PSE during pregnancy disrupts the existing balance in the bone and negatively affects ossification due to the dose increase. In conclusion, we present descriptive and novel data on the effects of PSE use during pregnancy on the bone development of rat fetal long bones.

Supersulfides support bone growth by promoting chondrocyte proliferation in the growth plates.

OBJECTIVES: While chondrocytes have mitochondria, they receive little O2 from the bloodstream. Sulfur respiration, an essential energy production system in mitochondria, uses supersulfides instead of O2. Supersulfides are inorganic and organic sulfides with catenated sulfur atoms and are primarily produced by cysteinyl tRNA synthetase-2 (CARS2). Here, we investigated the role of supersulfides in chondrocyte proliferation and bone growth driven by growth plate chondrocyte proliferation. METHODS: We examined the effects of NaHS, an HS-/H2S donor, and cystine, the cellular source of cysteine, on the proliferation of mouse primary chondrocytes and growth of embryonic mouse tibia in vitro. We also examined the effect of RNA interference acting on the Cars2 gene on chondrocyte proliferation in the presence of cystine. RESULTS: NaHS (30 µmol/L) enhanced tibia longitudinal growth in vitro with expansion of the proliferating zone of their growth plates. While NaHS (30 µmol/L) also promoted chondrocyte proliferation only under normoxic conditions (20 % O2), cystine (0.5 mmol/L) promoted it under both normoxic and hypoxic (2 % O2) conditions. Cars2 gene knockdown abrogated the ability of cystine (0.5 mmol/L) to promote chondrocyte proliferation under normoxic conditions, indicating that supersulfides produced by CARS2 were responsible for the cystine-dependent promotion of bone growth. CONCLUSIONS: The presented results indicate that supersulfides play a vital role in bone growth achieved by chondrocyte proliferation in the growth plates driven by sulfur respiration.

The effect of ionizing radiation on the fetal bone development in pregnant rats: Role of melatonin.

Radiation has been widely used in many business sectors over the last century. Our study investigated the possible teratogenic effects of radiation on the bones of rat fetuses and the protective effect of melatonin against these effects. In this study, 15 pregnant female Wistar albino rats were used. These rats were divided into four groups: the control group, melatonin group (10 mg/kg/day), radiation group (0.5 gray), radiation (0.5 gray) + melatonin group (10 mg/kg/day), and sham group (1 mm hanks/day). The skeletal system development of fetuses was examined with double skeletal and scanning electron microscope (SEM), histopathological methods. In our study, fetal weight, placental weight, and fetal morphometric values were found to be statistically significantly decreased in the radiation group compared to the control group (p < .05). In immünohistochemistry (IHC) analysis, alkaline phosphatase, and tartrate-resistant acid phosphatase) concentrations were found to be significantly lower in the radiation group compared to the other groups. In the SEM analysis, it was observed that the amount of calcium and sodium decreased when the radiation group was compared with the other groups. As a result, when exposed to ionizing radiation during pregnancy, melatonin has a protective feature against the negative effects of radiation on the bone development of fetuses. RESEARCH HIGHLIGHTS: In our study, fetuses obtained from pregnant rats exposed to ionizing radiation were examined. In this study, the effect of melatonin on bone development in fetuses exposed to gray ionizing radiation was investigated. There are few studies on our subject in the literature. We believe that our findings will contribute to other planned studies.

YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulation in murine bone development.

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.

Systems genetics and bioinformatics analyses using ESR1-correlated genes identify potential candidates underlying female bone development.

Estrogen receptor α (ESR1) is involved in E2 signaling and plays a major role in postmenopausal bone loss. However, the molecular network underlying ESR1 has not been explored. We used systems genetics and bioinformatics to identify important genes associated with Esr1 in postmenopausal bone loss. We identified ~2300 Esr1-coexpressed genes in female BXD bone femur, functional analysis of which revealed 'osteoblast signaling' as the most enriched pathway. PPI network led to the identification of 25 'female bone candidates'. The gene-regulatory analysis revealed RUNX2 as a key TF. ANKRD1 and RUNX2 were significantly different between osteoporosis patients and healthy controls. Sp7, Col1a1 and Pth1r correlated with multiple femur bone phenotypes in BXD mice. miR-3121-3p targeted Csf1, Ankrd1, Sp7 and Runx2. ß-estradiol treatment markedly increased the expression of these candidates in mouse osteoblast. Our study revealed that Esr1-correlated genes Ankrd1, Runx2, Csf1 and Sp7 may play important roles in female bone development.

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.