scholarly journals Early Detection of Tibial Cartilage Degradation and Cancellous Bone Loss in an Ovariectomized Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yinong Wang ◽  
Zhiwei Liu ◽  
Qing Wang ◽  
Qianjin Feng ◽  
Wufan Chen

This study aimed to investigate degradation of the articular cartilage and loss of the cancellous bone in an ovariectomized (OVX) rat model simulating early human menopausal stage. Fourteen health female Sprague-Dawley rats were randomly divided into two groups (n=7 per group): an OVX group that underwent bilateral ovariectomy to create an OVX model with low estrogen levels and a sham group in which only the periovarian fatty tissue was exteriorized. All the animals were sacrificed at 3 weeks after ovariectomy. The left tibiae were harvested. The articular cartilage at medial tibial plateau (MTP) and lateral tibial plateau (LTP) was assessed with quantitative high-frequency ultrasound. The cancellous bone was evaluated with micro-CT. The results indicated that, in comparison with the sham rats, the OVX rats exhibited significant alterations in acoustic parameters of the articular cartilage but insignificant changes in microarchitectural parameters of the cancellous bone in early stage of low estrogen levels. The results of this study suggest that cartilage degradation induced by estrogen reduction was detected earlier with quantitative ultrasound than that of the cancellous bone loss in 3 wk OVX rats.

1998 ◽  
Vol 274 (2) ◽  
pp. E328-E335 ◽  
Author(s):  
C. K. Lea ◽  
A. M. Flanagan

The effect of androstenedione (ADIONE) slow-release pellets on cancellous bone volume (BV/TV) at the tibial metaphysis was investigated in ovariectomized (OVX) rats at various times from 21 to 180 days. Plasma levels of ADIONE and testosterone (T) in OVX rats were significantly reduced at 21 days and were restored close to levels in the sham rats with the 1.5-mg ADIONE pellet. OVX animals with and without ADIONE pellets resulted in close to a 50% reduction in BV/TV by day 21. By day 180, OVX rats had only ∼5% BV/TV, whereas that in ADIONE-treated OVX rats was significantly greater at ∼12%. The reduced BV/TV was associated with increased bone resorption and formation. In a separate 90-day experiment, we found that the antiandrogen, Casodex, abrogated the ADIONE-induced skeletal-protective effect in OVX rats, whereas the antiaromatase, Arimidex, had no effect. This provides evidence that ADIONE protects against the development of osteopenia in the estrogen-deficient rat and mediates its effect through androgens and not estrogens.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1260 ◽  
Author(s):  
Marta Anna Szychlinska ◽  
Rosa Imbesi ◽  
Paola Castrogiovanni ◽  
Claudia Guglielmino ◽  
Silvia Ravalli ◽  
...  

Deficiency in vitamin D (Vit D) has been widely associated with several musculoskeletal diseases. However, the effects of the exogenous Vit D supplementation are still unclear in the prevention of the latter, especially in the cartilage developmental period. The aim of this study was to compare the effects of Vit D supplementation and restriction on the articular cartilage development in healthy young sedentary rats. To this aim, twelve nine-week-old healthy Sprague–Dawley male rats were subjected to Vit D-based experimental diets: R, with a content in Vit D of 1400 IU/kg; R-DS, with a Vit D supplementation (4000 IU/kg); R-DR, with a Vit D restriction (0 IU/kg) for 10 weeks. The morphology, thickness and expression of cartilage-associated molecules such as collagen type II/X, lubricin and Vit D receptor (VDR), were assessed. Histological, histomorphometric and immunohistochemical evaluations were made on rat tibial cartilage samples. In the present experimental model, restriction of Vit D intake induced: The lower thickness of cartilage compared both to R (p = < 0.0001) and R-DS (p = < 0.0001); reduction of proteoglycans in the extracellular matrix (ECM) compared both to R (p = 0.0359) and R-DS (p = < 0.0001); decreased collagen II (Col II) with respect both to R (p = 0.0076) and R-DS (p = 0.0016); increased collagen X (Col X) immunoexpression when compared both to R (p = < 0.0001) and R-DS (p = < 0.0001), confirming data from the literature. Instead, supplementation of Vit D intake induced: Higher cartilage thickness with respect both to R (p = 0.0071) and R-DR (p = < 0.0001); increase of ECM proteoglycan deposition compared both to R (p = 0.0175) and R-DR (p = < 0.0001); higher immunoexpression of lubricin with respect both to R (p = 0.001) and R-DR (p = 0.0008). These results suggest that Vit D supplementation with diet, already after 10 weeks, has a favorable impact on the articular cartilage thickness development, joint lubrication and ECM fibers deposition in a young healthy rat model.


2019 ◽  
Vol 70 (2) ◽  
pp. 1541
Author(s):  
C. PASSALI ◽  
A. PATSAKI ◽  
P. LELOVAS ◽  
N. ALIGIANNIS ◽  
M. MAKROPOULOU ◽  
...  

The aim of this study was to examine the effect of Red Wine Polyphenols (RWPs) extract on bone mineral density (BMD) in the ovariectomized (OVX) rat model. Thirty-five 10-month-old Wistar rats were separated into controls (CTRL), OVX and OVX plus RWPs in their drinking water (dose, 50 mg/kg body weight per day), starting immediately after OVX for 6 months. Βody and uterine weight, BMD of the tibia at baseline, 3 and 6 months post-OVX, and 3-pointing bending of the femur, were examined. Statistical comparison of the total tibia BMD within groups during the study period showed a significant reduction in the OVX and OVX+RWPs groups both from baseline to 3 and 6 months and from 3 to 6 months, whereas in the CTRL group, there was no significant change. For the proximal tibial metaphysis, comparison of BMD percentage changes from baseline to 3 months and 6 months and from 3 to 6 months revealed highly statistical differences between OVX and OVX+RWPs groups (P = 0.000). OVX induced a significant reduction of biomechanical parameters as expected; the 3-point bending test showed that the maximum force before fracture, energy absorption and fracture stress significantly increased in the OVX group treated with RWPs compared with the nontreated OVX rats (P = 0.048, P = 0.002 and P = 0.003, respectively). Dietary intake of RWPs for 6 months significantly prevented trabecular bone loss and improved bone strength in estrogen-deficient ovariectomized rats.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyewon Park ◽  
Jinpyo Hong ◽  
Yuhua Yin ◽  
Yongbum Joo ◽  
Youngmo Kim ◽  
...  

Abstract Because inflammation in osteoarthritis (OA) is related to the Toll-like receptor 4 (TLR4) signaling cascades, TLR4 is a reasonable target for developing therapeutics for OA. Thus, we investigated whether TAP2, a peptide antagonist of TLR4, reduces the monoiodoacetate (MIA)-induced arthritic pain and cartilage degradation in rats. TLR4 expression of human OA chondrocytes and synoviocytes and the knee joint tissue of MIA-induced arthritis were evaluated. MIA-induced arthritic model using Sprague–Dawley rats (6 week-old-male) were treated with TAP2, a TLR4 antagonist, and evaluated with behavioral test, immunohistochemistry, and quantitative PCR. TLR4 was highly expressed in the knee joints of patients with OA and the MIA-induced rat model. Further, a single intraarticular injection of TAP2 (25 nmol/rat) molecules targeting TLR4 on day 7 after MIA injection dramatically attenuated pain behavior for about 3 weeks and reduced cartilage loss in the knee joints and microglial activation in the spinal dorsal horns. Likewise, the mRNA levels of TNFα and IL-1β, reactive oxygen species, and the expression of MMP13 in the knee joints of TAP2-treated rats was significantly decreased by TAP2 treatment compared with the control. Moreover, interestingly, the duration of OA pain relief by TAP2 was much longer than that of chemical TLR4 antagonists, such as C34 and M62812. In conclusion, TAP2 could effectively attenuate MIA-induced arthritis in rats by blocking TLR4 and its successive inflammatory cytokines and MMP13. Therefore, TAP2 could be a prospective therapeutic to treat patients with OA.


Endocrinology ◽  
2003 ◽  
Vol 144 (3) ◽  
pp. 785-792 ◽  
Author(s):  
J. D. Sibonga ◽  
S. Lotinun ◽  
G. L. Evans ◽  
V. S. Pribluda ◽  
S. J. Green ◽  
...  

In three experiments, we evaluated the pharmacological effects of 2-methoxyestradiol (2ME2) on several estrogen target tissues. Experiment 1: we gavaged recently ovariectomized (OVX) 9.5-wk-old rats with 2ME2 at doses of 0, 0.1, 1, 4, 20, and 75 mg/kg in a 21-d dose-response study. 2ME2 reduced body weight and serum cholesterol, increased uterine weight and epithelial cell height, and inhibited longitudinal and radial bone growth compared with values in the untreated OVX rat. All doses of 2ME2 maintained cancellous bone mass at the baseline level, the lowest effective dose being 20-fold less than a uterotrophic dose. Experiment 2: in an 8-wk experiment in adult OVX rats, a nonuterotrophic dose of 2ME2 (4 mg/kg·d) suppressed body weight gain, inhibited bone formation in cancellous bone and partially prevented bone loss in the tibial metaphysis. Experiment 3: in weanling rats, ICI 182,780 did not antagonize the effect of 2ME2. We conclude that 2ME2 antagonizes the skeletal changes that follow OVX at doses that have minimal or no effects in the uterus in both young and adult rats; 2ME2 does not appear to act via estrogen receptors and is active on bone at doses well below those required for tumor suppression in mice. 2ME2, through a novel pathway, may be a useful alternative to conventional hormone replacement therapy for prevention of postmenopausal bone loss.


Author(s):  
Zhao ◽  
Bu ◽  
Chen

Estrogen deficiency frequently leads to a fall in estrogen receptor- (ER) numbers and then reduces the skeletal response to mechanical strain. It, however, is still unclear whether phytoestrogen administration will enhance the effects of exercise on the estrogen-deficient bone loss. This study aimed to determine the effect of Icariin treatment on the response of osteogenic formation to exercise in ovariectomized (OVX) rats. Thirty-two 3-month old female Sprague–Dawley rats were randomly allocated into four groups: (1) Sham-operated (SO); (2) OVX; (3) OVX plus exercise (EX); and (4) OVX plus exercise and Icariin (EI). After 8-week interventions, the rats were killed and samples were collected for bone morphometry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. EI interventions showed a greater improvement for the OVX-induced bone loss and the elevated serum tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) compared with EX only. Both EX and EI interventions bettered the OVX-related reduction of BV/TV and trabecular number and thickness, and decreased the enlargement of trabecular bone separation (Tb. Sp); the improvement for BV/TV and Tb. Sp was greater in EI group. Furthermore, EX and EI treatment significantly increased the number of ALP+ cells and mineralized nodule areas compared with OVX group; the change was higher in EI group. Additionally, in comparison to OVX rats, the protein and mRNA expression of -catenin, phosphorylated-Akt (p-Akt) or Akt, ER, and Runt-related transcription factor 2 (Runx2) in osteoblasts were elevated in EX and EI intervention rats, with greater change observed in EI group. The upregulated -catenin and Akt mRNA levels in EX and EI groups was depressed by ICI182780 treatment, and the difference in -catenin and Akt mRNA levels between EX and EI groups was no longer significant. Conclusively, the combination of Icariin and exercise significantly prevent OVX-induced bone loss and increase osteoblast differentiation and the ability of mineralization compared with exercise alone; the changes might be regulated partly by ER/Akt/-catenin pathway.


2021 ◽  
Author(s):  
Nima Montazeri-Najafabady ◽  
Younes Ghasemi ◽  
Mohammad Hossein Dabbaghmanesh ◽  
Yousef Aashoori ◽  
Pedram Talezadeh ◽  
...  

Abstract Background Postmenopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations and ovariectomized. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global BMC, Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMC. We found Bacillus coagulans supernatant meaningfully enriched tibia BMC. Conclusion Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254383
Author(s):  
Ikufumi Takahashi ◽  
Keisuke Takeda ◽  
Taro Matsuzaki ◽  
Hiroshi Kuroki ◽  
Masahiro Hoso

The purpose of this study was to clarify the histological effect of reducing the loading to knee on cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis (OA) using a post-traumatic rat model. Ten male rats were randomly allocated into two experimental groups: OA induction by surgical destabilization of medial meniscus (DMM, OA group) and hindlimb suspension after OA induction by DMM (OAHS group). The articular cartilage, osteophyte formation, and synovial membrane in the medial tibiofemoral joint were analyzed histologically and histomorphometrically at 2 and 4 weeks after surgery. The histological scores and changes in articular cartilage and osteophyte formation were significantly milder and slower in the OAHS group than in the OA group. At 2 and 4 weeks, there were no significant differences in cartilage thickness and matrix staining intensity between both the groups, but chondrocytes density was significantly lower in the OA group. Synovitis was milder in OAHS group than in OA group at 2 weeks. Reducing knee joint loading inhibited histological OA changes in articular cartilage, osteophyte formation, and synovial inflammation. This result supports the latest clinical guidelines for OA treatment. Further studies using biochemical and mechanical analyses are necessary to elucidate the mechanism underlying delayed OA progression caused by joint-load reduction.


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