scholarly journals Probiotics (Bifidobacterium longum) Increase Bone Mass Density and UpregulateSparcandBmp-2Genes in Rats with Bone Loss Resulting from Ovariectomy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Kolsoom Parvaneh ◽  
Mahdi Ebrahimi ◽  
Mohd Redzwan Sabran ◽  
Golgis Karimi ◽  
Angela Ng Min Hwei ◽  
...  

Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects ofBifidobacterium longum(B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL ofB. longum108–109colony forming units (CFU)/mL).B. longumwas given once daily for 16 weeks, starting from 2 weeks after the surgery. TheB. longumsupplementation increased (p<0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p<0.05) the expression ofSparcandBmp-2genes.B. longumalleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.


2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.


Author(s):  
Kusworini Handono ◽  
BP Putra Suryana ◽  
Sulistyorini Sulistyorini

Rheumatoid Arthritis (RA) is a systemic autoimmune disease accompanied by decreasing bone mass density and ultimately leads toosteoporosis. The cause of decreased bone mass density is still unknown, but the inflammation has been suspected as an important factor.The correlation between the severity of inflammation with the decrease in bone mass density in Indonesian RA patients has not been muchstudied. The purpose of this study was to know the assessment in the correlation between levels of C-reactive protein (CRP), Tumour NecrosisFactor-α (TNFα) and bone mineral density (BMD) with bone resorption marker CTx-1 β-Cross Laps in premenopausal RA patients.Thisobservational study using cross sectional design, was carried out in the Rheumatology Clinic and Central Laboratory of RSSA, Malang fromAugust 2009 until October 2010. All 47 RA patients were diagnosed according to revised of the 1997 American College of Rheumatology(ACR). Measurement of CRP levels uses turbidimetry method, TNF-α and CTX-1 β-Cross Laps levels using ELISA methods and the measurementof BMD using DEXA. The results of this study showed mean levels of CRP were 4.288±1.775 g/L, TNF-α were 322.077±275.248 pg/mLand CTX-1 β-Cross Laps were 0.588±0.139 ng mL. The correlation of CRP and TNF-α levels with CTX-1 β-Cross Laps level were r=0.5832,p=0.453 and r=0.615, p=0.041. Correlation of CTX-1 β-Cross Laps level and Femoral Neck BMD was r=–0.469, p=0.143 and r=0.248,p=0.799 for L average BMD. There was no correlation between CRP level and BMD results with bone resorption marker CTX-1 β-Cross Laps,but there is a significant correlation between high levels of TNFα with CTX-1 β-Cross Laps. It seems that TNF-α appears to be contributed tothe decrease of bone mass density in RA patients.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lu-lin Liu ◽  
Gong-wen Liu ◽  
Hui Liu ◽  
Kai Zhao ◽  
You-jia Xu

Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.


2009 ◽  
Vol 202 (2) ◽  
pp. 317-325 ◽  
Author(s):  
Idris Mohamed ◽  
James K Yeh

Long-term aromatase inhibitor use causes bone loss and increases fracture risk secondary to induced estrogen deficiency. We postulated that alfacalcidol (A; vitamin D3 analog) could help prevent the Letrozole (L)-induced mineral bone loss. Fifty intact 1-month-old female rats were randomly divided into basal group; age-matched control group (AMC); L group: oral administration of 2 mg/kg per day; A group: oral administration of 0.1 μg/kg per day; and group L+A for a period of 8 weeks. Eight-week administration of L resulted in a significant increase in body weight, bone length, bone area, bone formation, and bone resorption activities when compared with the AMC group. However, the bone mass and bone mineral density (BMD) were significantly lower than the AMC group. Serum levels of testosterone, LH, FSH, and IGF-1 were significantly higher and serum estrone and estradiol were lower along with a decrease in ovary+uterus horn weight, when compared with the AMC groups. None of those parameters were affected by A treatment, except suppression of bone resorption activities and increased trabecular bone mass and femoral BMD, when compared with the AMC group. Results of L+A combined intervention showed that bone length, bone area, and bone formation activities were higher than the AMC group, and the bone resorption activities were lower and BMD was significantly higher than that of the L group. This study demonstrates that the combined intervention of L and A not only enhances bone growth, but also increases bone density, and the effects of L and A are independent and additive.


Author(s):  
Mr. Sujin Thomas

Bone is living, growing tissue. It is made mostly of collagen, a protein that provides a soft framework, and calcium phosphate, a mineral that adds strength and hardens the framework. This combination of collagen and calcium makes bone both flexible and strong, which in turn helps bone to withstand stress.1 More than 99 percent of the body’s calcium is contained in the bones and teeth. The remaining 1 percent is found in the blood. Throughout one’s lifetime, old bone is removed (resorption) and new bone is added to the skeleton (formation). During childhood and teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation outpaces resorption until peak bone mass (maximum bone density and strength) is reached around age 30. After that time, bone resorption slowly begins to exceed bone formation. For women, bone loss is fastest in the first few years after menopause, and it continues into the postmenopausal years. Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures of the hip, spine, and wrist. Osteoporosis is more likely to develop if you did not reach optimal peak bone mass during your bone-building years. Women are at a greater risk than men, especially women who are thin or have a small frame, as are those of advanced age. Women who are postmenopausal, including those who have had early or surgically induced menopause, or abnormal or absence of menstrual periods, are at greater risk. Cigarette smoking, eating disorders such as anorexia nervosa or bulimia, low amounts of calcium in the diet, heavy alcohol consumption, inactive lifestyle, and use of certain medications, such as corticosteroids and anticonvulsants, are also risk factors for osteoporopsis.2 The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. In normal bone, matrix remodeling of bone is constant; up to 10% of all bone mass may be undergoing remodeling at any point in time. The process takes place in bone multicellular units (BMUs) as first described by Frost & Thomas in 1963. Osteoclasts are assisted by transcription factor PU.1 to degrade the bone matrix, while osteoblasts rebuild the bone matrix. Low bone mass density can then occur when osteoclasts are degrading the bone matrix faster than the osteoblasts are rebuilding the bone. The three main mechanisms by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excessive bone resorption, and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue. Hormonal factors strongly determine the rate of bone resorption; lack of estrogen (e.g. as a result of menopause) increases bone resorption, as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones.this leads to weakening and softening of bones the bones become soft and it will prone to get fracture or collapse.


2013 ◽  
Vol 16 (1) ◽  
pp. 24-28
Author(s):  
S S Rodionova ◽  
T N Turgumbayev

In a comparative study we investigated the influence of a combination of alendronate and alfacalcidol on the dynamics of bone mass density (BMD) at the site attached to the femoral component of endoprosthesis in total hip replacement in patients with systemic osteoporosis. Evaluation of performance of pharmacotherapy in the postoperative period on osteoporosis, systemic osteoporosis, sustained BMD deficit at Gruen regions confirmed that the essential component of osteointegration at the «implant-bone» site during the period of physiological adaptive remodeling after arthroplasty in women suffering from systemic osteoporosis is the pharmacological correction of the intensity of bone resorption in post-operative period.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3210
Author(s):  
Farida S. Nirmala ◽  
Hyunjung Lee ◽  
Ji-Sun Kim ◽  
Taeyoul Ha ◽  
Chang Hwa Jung ◽  
...  

Although drug therapies are available for postmenopausal osteoporosis, these drugs are not free of side effects and long-term adherence to them are low. A safe and effective nutritional approach to counter postmenopausal osteoporosis is an important research goal. We fed ovariectomized (OVX) Sprague–Dawley rats a diet supplemented with 1% or 2% green tomato extract (GTE). After 12 weeks, micro-computed tomography scans revealed that GTE supplementation effectively prevented distal femur bone loss. This prevention was due to improved bone formation and suppressed bone resorption as observed by the regulation of osteoblast and osteoclast activities. GTE supplementation also improved bone formation through Bmp2-Smad 1/5/8-Runx2 signaling, while bone resorption was regulated by the receptor activator of nuclear factor kappa-B (RANKL)/osteoprogeterin (OPG) pathway. These results suggest that GTE supplementation prevents severe postmenopausal bone loss by maintaining the regulation of bone homeostasis in OVX rats. GTE as a diet supplement might be a potential novel alternative for the prevention of postmenopausal osteoporosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Zhiguo Zhang ◽  
Lihua Xiang ◽  
Dong Bai ◽  
Xiaowei Fu ◽  
Wenlai Wang ◽  
...  

The aims of this study were to evaluate the osteoprotective effect of aqueous extract fromRhizoma Dioscoreae(RDE) on rats with ovariectomy- (OVX-) induced osteopenia. Our results show that RDE could inhibit bone loss of OVX rats after a 12-week treatment. The microarray analysis showed that 68 genes were upregulated and that 100 genes were downregulated in femurs of the RDE group rats compared to those in the OVX group. The Ingenuity Pathway Analysis (IPA) showed that several downregulated genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Sost, Lrp6, Tcf7l2, and Alpl) and the RANKL/RANK signaling pathway (Map2k6 and Nfatc4). These results revealed that the mechanism for an antiosteopenic effect of RDE might lie in the synchronous inhibitory effects on both the bone formation and the bone resorption, which is associated with modulating the Wnt/β-catenin signaling and the RANKL/RANK signaling.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Supitra Namhong ◽  
Kannikar Wongdee ◽  
Panan Suntornsaratoon ◽  
Jarinthorn Teerapornpuntakit ◽  
Ruedee Hemstapat ◽  
...  

Abstract Osteoarthritis (OA) leads to joint pain from intraarticular inflammation with articular cartilage erosion, deterioration of joint function and abnormal subchondral bone structure. Besides aging, chronic repetitive joint injury is a common risk factor in young individuals. Nevertheless, whether OA is associated with bone loss at other skeletal sites is unclear. Since OA-associated proinflammatory cytokines—some of which are osteoclastogenic factors—are often detected in the circulation, we hypothesized that the injury-induced knee OA could result in widespread osteopenia at bone sites distant to the injured knee. Here we performed anterior cruciate ligament transection (ACLT) to induce knee OA in one limb of female Sprague–Dawley rats and determined bone changes post-OA induction by micro-computed tomography and computer-assisted bone histomorphometry. We found that although OA modestly altered bone density, histomorphometric analyses revealed increases in bone resorption and osteoid production with impaired mineralization. The bone formation rate was also reduced in OA rats. In conclusions, ACLT in young growing rats induced microstructural defects in the trabecular portion of weight-bearing (tibia) and non-weight-bearing bones (L5 vertebra), in part by enhancing bone resorption and suppressing bone formation. This finding supports the increasing concern regarding the repetitive sport-related ACL injuries and the consequent bone loss.


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