scholarly journals Reconstitution of the host holobiont in germ-free rats acutely increases bone growth and affects marrow cellular content

2020 ◽  
Author(s):  
PJ Czernik ◽  
RM Golonka ◽  
S Chakraborty ◽  
BS Yeoh ◽  
A Abokor ◽  
...  
Keyword(s):  
Bone Growth ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Male Rats ◽  
Bone Lengthening ◽  
Mineral Density ◽  
Growth Plate Chondrocytes ◽  
Germ Free ◽  
Hepatic Expression ◽  
Short Term Exposure

AbstractIn recent years there has been growing evidence regarding the effect of microbiota on the skeletal growth and homeostasis. Here we present, for the first time, accelerated longitudinal and radial bone growth in young (7-week-old) germ-free male rats after short-term exposure to a newly established gut microbiota. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in tibia diaphysis. In addition, the number of small-in-size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats. The observed changes in bone status were paralleled with a positive shift in microbiota composition towards short chain fatty acids (SCFA)-producing microbes, which reflected a dramatic increase in cecal concentration of SCFA, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels, implicating an involvement of the somatotropic axis. Increased serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase and resembled reversal of dysbiosis in adolescence, which is marked by rapid skeletal expansion. These findings may help in developing microbiota-based therapeutics to combat bone related disorders resulting from hormonal defects and/or malnutrition in children and adolescence.

Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content

2021 ◽  
Author(s):  
Piotr J Czernik ◽  
Rachel M. Golonka ◽  
Saroj Chakraborty ◽  
Beng San Yeoh ◽  
Ahmed A Abokor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Bone Growth ◽  
Elevated Serum ◽  
Male Rats ◽  
Bone Lengthening ◽  
Mineral Density ◽  
Germ Free ◽  
Hepatic Expression ◽  
Gut Colonization

Integration of microbiota in a host begins at birth and progresses during adolescence, forming a multidirectional system of physiologic interactions. Here, we present an instantaneous effect of natural, bacterial gut colonization on the acceleration of longitudinal and radial bone growth in germ-free born, 7-week-old male rats. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. In addition, the number of small in size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats indicating that not only bone mass but also bone marrow environment is under control of gut microbiota signaling. The changes in bone status paralleled with a positive shift in microbiota composition toward short chain fatty acids (SCFA)-producing microbes and a considerable increase in cecal SCFA concentrations, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels. Elevated serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase. Overall, the presented model of conventionalized germ-free rats could be used to study microbiota-based therapeutics for combatting dysbiosis-related bone disorders.

scholarly journals Gut microbiota induce IGF-1 and promote bone formation and growth

2016 ◽  
Vol 113 (47) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Jing Yan ◽  
Jeremy W. Herzog ◽  
Kelly Tsang ◽  
Caitlin A. Brennan ◽  
Maureen A. Bower ◽  
...  
Keyword(s):  
Bone Formation ◽  
Gut Microbiota ◽  
Bone Mass ◽  
Bone Growth ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Skeletal Growth ◽  
Microbial Colonization ◽  
Adult Mice ◽  
Specific Pathogen

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

scholarly journals Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

2021 ◽  
Vol 28 (4) ◽  
pp. 307-316
Author(s):  
Majed G. Alrowaili ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Mohamed S. Serria ◽  
Hussein Abdellatif ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Bone Mineral ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Intermittent Fasting ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Trap 5B

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

scholarly journals The JAK1/STAT3/SOCS3 axis in bone development, physiology, and pathology

2020 ◽  
Vol 52 (8) ◽  
pp. 1185-1197 ◽  
Author(s):  
Natalie A. Sims
Keyword(s):  
Bone Growth ◽  
Bone Structure ◽  
Bone Development ◽  
Osteoclast Formation ◽  
Bone Lengthening ◽  
Growth Plate Chondrocytes ◽  
Paracrine Factors ◽  
Stat3 Signaling ◽  
Skeletal Defects ◽  
Normal Differentiation

Abstract Bone growth and the maintenance of bone structure are controlled by multiple endocrine and paracrine factors, including cytokines expressed locally within the bone microenvironment and those that are elevated, both locally and systemically, under inflammatory conditions. This review focuses on those bone-active cytokines that initiate JAK–STAT signaling, and outlines the discoveries made from studying skeletal defects caused by induced or spontaneous modifications in this pathway. Specifically, this review describes defects in JAK1, STAT3, and SOCS3 signaling in mouse models and in humans, including mutations designed to modify these pathways downstream of the gp130 coreceptor. It is shown that osteoclast formation is generally stimulated indirectly by these pathways through JAK1 and STAT3 actions in inflammatory and other accessory cells, including osteoblasts. In addition, in bone remodeling, osteoblast differentiation is increased secondary to stimulated osteoclast formation through an IL-6-dependent pathway. In growth plate chondrocytes, STAT3 signaling promotes the normal differentiation process that leads to bone lengthening. Within the osteoblast lineage, STAT3 signaling promotes bone formation in normal physiology and in response to mechanical loading through direct signaling in osteocytes. This activity, particularly that of the IL-6/gp130 family of cytokines, must be suppressed by SOCS3 for the normal formation of cortical bone.

scholarly journals Impact of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Bone Mineral Content in a Rat Model of Male Hypogonadism

2020 ◽  
Vol 7 (4) ◽  
pp. 185
Author(s):  
Hussein F. Sakr ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ammar Boudaka ◽  
Lashin S. Lashin
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral Content ◽  
Bone Mineral ◽  
Mineral Content ◽  
Serum Levels ◽  
Male Rats ◽  
Type I ◽  
Male Hypogonadism ◽  
Mineral Density ◽  
Trap 5B

Objectives: The present study examined the effect DHEA (dehydroepiandrosterone) on bone mineral content (BMC) and bone mineral density (BMD) and biomarkers of bone remodeling in orchidectomized male rats. Material and Methods: A total of 32 male rats were divided equally into four groups (n = 8): (i) control group (C), (ii) control treated with DHEA (Control + DHEA), (iii) orchidectomized (ORCH) group that underwent bilateral orchidectomy and (iv) orchidectomized (ORCH) rats treated with DHEA (ORCH+DHEA). DHEA treatment started 4 weeks after orchidectomy and continued for 12 weeks. After 12 weeks the bone mineral density (BMD) and bone mineral content (BMC) were assayed in the tibia and femur of the right hind limb of each rat. We also measured the serum levels of the bone turnover markers deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTx), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRAP-5b) and osteocalcin (OC) as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG). Results: Orchidectomy in rats caused significant reduction in BMD, BMC, serum levels of testosterone, PTH (parathyroid hormone), OPG, OC and ALP with significant rise in serum levels of TRAP-5B, RANK, Dpd and NTx1 (p < 0.05). On the other hand, DHEA therapy for 12 weeks caused significant improvement in all studied parameters except NTx1 (p < 0.05). Conclusions: DHEA corrected hypogonadism-induced osteoporosis in male rats probably via inhibiting osteoclastogenesis, stimulating the activity of osteoblasts and stimulating the secretion of PTH and testosterone.

scholarly journals Long-term effects on bone of postnatal immunization against GHRH in female and male rats

2003 ◽  
Vol 177 (1) ◽  
pp. 93-100 ◽  
Author(s):  
V Sibilia ◽  
AE Rigamonti ◽  
F Pagani ◽  
N Lattuada ◽  
F Guidobono ◽  
...  
Keyword(s):  
Bone Mineral ◽  
Bone Growth ◽  
Passive Immunization ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Long Term Effects ◽  
Mineral Density ◽  
Male And Female Rats ◽  
Igf I

The effects of neonatal passive immunization against GHRH on bone was examined in male and female rats. Pups were treated subcutaneously with GHRH-antiserum (GHRH-Ab) from day 1 to day 10 of age. Bone mineral content (BMC) and bone mineral density (BMD) were evaluated at monthly intervals until 7 months. Markers of bone resorption (urinary lysylpyridinoline, LP), bone formation (serum osteocalcin, OC) and serum IGF-I were measured at 2, 3 and 7 months. In male rats, GHRH-Ab did not modify BMC and BMD when compared with controls. In contrast, female rats demonstrated lower whole body and femoral BMC and BMD from 2 to 7 months of age. Reduced bone growth in the females was associated with lower IGF-I levels than controls at 2 and 3 months of age, whereas in males IGF-I titers did not change during the period of the study. LP excretion was higher in GHRH-Ab-treated rats at 2 and 3 months in both sexes. In females, no difference in OC values was recorded, whereas in GHRH-Ab-treated males, there was an increase in OC levels at 2 and 3 months. These data indicate that transient GHRH deprivation induces an osteopenic effect in female rats which is not evident in male rats.

EFFECT OF BILATERAL CRYPTORCHIDISM UPON PITUITARY AND SERUM LEVELS OF LH AND FSH IN SEXUALLY MATURING MALE RATS

1975 ◽  
Vol 80 (1_Suppla) ◽  
pp. S87
Author(s):  
M. Eichner ◽  
K. Rager ◽  
A. Attanasio ◽  
D. Gupta
Keyword(s):  
Serum Levels ◽  
Male Rats ◽  
Bilateral Cryptorchidism

REPRODUCTIVE TOXICITY OF CHLORPYRIFOS, CYPERMETHRIN AND THEIR INTERACTION IN MALE ALBINO RATS

2018 ◽  
pp. 69-86
Author(s):  
Asmaa ELnamaky ◽  
Amal Halawa ◽  
Mamdouh Abouelmaged
Keyword(s):  
Reproductive Toxicity ◽  
Prostatic Acid Phosphatase ◽  
Serum Levels ◽  
Reproductive Organs ◽  
Male Rats ◽  
Albino Rats ◽  
Glutathione S Transferase ◽  
Significant Drop ◽  
Sperm Abnormalities ◽  
Pituitary Glands

he present work was designed to investigate the reproductive toxicity induced by oral administration of chlorpyrifos (CPF), cypermethrin (CYP) and their combination in adult male albino rats. Forty mature male albino rats were separated into four groups (10 each), the first group was used as control, while second, third and fourth groups received orally 1/20 LD50 of CPF (10 mg/kg b.wt), 1/20 LD50 of CYP (17.22 mg/kg b.wt) and 1/40 LD50 of CPF plus 1/40 LD50 of CYP (5 mg/kg b.wt CPF plus 8.61 mg/kg b.wt CYP) respectively for 26 days. The results revealed that exposure to CPF and/or CYP induced a significant decrease in the reproductive organs weight. Moreover, a significant decrease in spermatic picture (sperm cell concentration and viability) was observed with high percent of sperm abnormalities. Serum levels of testosterone and pituitary gonadotropins (FSH and LH) have been declined significantly in all treated groups. Significant elevations were observed in malondialdehyde and nitric oxide concentrations, while antioxidant enzymes superoxide dismutase and glutathione-S-transferase activities were decreased significantly as a result of induced oxidative stress. A significant drop in prostatic acid phosphatase activity was observed. Additionally, the results showed some histopathological alterations in the reproductive organs as well as neurological lesions in brain and pituitary glands. In conclusion, CPF and CYP induce deleterious effects on reproductive efficiency of male rats which reflect more obvious impacts when both combined

scholarly journals Circulating bioactive sclerostin levels in an Austrian population-based cohort

2021 ◽  
Author(s):  
Katharina Kerschan-Schindl ◽  
Ursula Föger-Samwald ◽  
Andreas Gleiss ◽  
Stefan Kudlacek ◽  
Jacqueline Wallwitz ◽  
...  
Keyword(s):  
Serum Levels ◽  
Population Based ◽  
Negative Regulator ◽  
Total Serum ◽  
Mineral Density ◽  
Cross Sectional ◽  
Robust Parameter ◽  
Austrian Population ◽  
Different Levels

Summary Background Circulating serum sclerostin levels are supposed to give a good estimation of the levels of this negative regulator of bone mass within bone. Most studies evaluating total serum sclerostin found different levels in males compared to females and in older compared to younger subjects. Besides an ELISA detecting total sclerostin an ELISA determining bioactive sclerostin has been developed. The aim of this study was to investigate serum levels of bioactive sclerostin in an Austrian population-based cohort. Methods We conducted a cross-sectional observational study in 235 healthy subjects. Using the bioactive ELISA assay (Biomedica) bioactive sclerostin levels were evaluated. Results Serum levels of bioactive sclerostin were higher in men than in women (24%). The levels correlated positively with age (r = 0.47). A positive correlation could also be detected with body mass index and bone mineral density. Conclusion Using the ELISA detecting bioactive sclerostin our results are consistent with data in the literature obtained by different sclerostin assays. The determination of sclerostin concentrations in peripheral blood thus appears to be a robust parameter of bone metabolism.

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