scholarly journals A Novel Peptide, CK2.3, Improved Bone Formation in Ovariectomized Sprague Dawley Rats

2020 ◽  
Vol 21 (14) ◽  
pp. 4874 ◽  
Author(s):  
Linda Sequeira ◽  
John Nguyen ◽  
Liyun Wang ◽  
Anja Nohe

Osteoporosis is a bone disease that has no definite cure. Current treatments for osteoporosis are divided into two categories: anti-resorptive and anabolic. However, these treatments are not perfect and have considerable risks. In addition, bone quality often declines over time with these treatments. We designed a peptide, CK2.3, that has both anabolic and anti-resorptive effects on bone. We reported that CK2.3 induced osteoblastic mineralization, promoted bone formation, and suppressed osteoclastogenesis in vivo. The effect of CK2.3 to rescue an osteoporosis phenotype model has never been shown. In this study, we demonstrated the effect of CK2.3 in ovariectomized rats, a standard model of osteoporosis. We systemically injected CK2.3 at 2.3 µg/kg each day for five consecutive days. Micro-computed tomography indicated that CK2.3 increased bone mineral density, (bone volume/tissue volume) BV/TV and (trabecular number) TbN, and decreased (trabecular space) TbSp in the femoral head. Similarly, single photon absorptiometry showed that treatment with CK2.3 increased bone mineral density in the lumbar spine and the pelvis. Additionally, we observed increased femoral shaft stiffness with ovariectomized rats treated with CK2.3. We also detected no significant changes in the weight of organs such as the heart, lung, liver, kidney, and spleen. An advantage of CK2.3 over current treatments was that it not only promoted bone formation but also improved fracture resistance. In conclusion, we demonstrated CK2.3 as a new anabolic treatment for osteoporosis.

2001 ◽  
Vol 91 (4) ◽  
pp. 1663-1668 ◽  
Author(s):  
K. J. Hart ◽  
J. M. Shaw ◽  
E. Vajda ◽  
M. Hegsted ◽  
S. C. Miller

Weight-bearing exercise is traditionally recommended for improving bone health in postmenopausal women. Effects of swim exercise were studied as an alternative to weight-bearing exercise in ovariectomized rats. Rats in a swim group (Sw, n = 8) swam for 12 wk, 5 days/wk for 60 min per session. A control group (Con, n = 9) engaged in no structured exercise. Femurs were analyzed for bone mineral density and for bone mineral content by dual energy X-ray absorptiometry, biomechanical properties by three-point bending (Instron), and bone structure and formation by histomorphometry. Food intake did not differ among groups. Final body weights were significantly lower in Sw compared with Con ( P< 0.05). Swimmers had significantly greater femoral shaft bone mineral density and content ( P < 0.05) compared with Con. Femurs of the Sw group had greater mechanical properties ( P< 0.05) compared with Con. Histomorphometric data were significantly better in the Sw group compared with Con after the 12-wk intervention ( P < 0.05). In conclusion, data from this study demonstrate some beneficial effects of swim exercise on bone structure, turnover, and strength.


2013 ◽  
Vol 302 ◽  
pp. 26-30
Author(s):  
Fa Ming Tian ◽  
Liu Zhang ◽  
Hui Zhang ◽  
Jie Zheng ◽  
Da Cheng Han ◽  
...  

Simvastatin, as one of the HMG-CoA reductase inhibitors for lowering lipids, has been demonstrated its potential benefit in bone formation, which was, however, conflicting and inconclusive in vivo studies. Thus, we performed this study to assess the in vivo effects of simvastatin on bone formation. Six-week old rats were administered with simvastatin (20 mg/kg/d) or vehicle for 6 or 9 weeks. All animals were sacrificed one day after the final administration. The left femora were removed for the measurement of bone histomorphometry and bone mineral density (BMD).Compared to the control groups, on both 6th week and 9th week, bone mineral density and bone histomorphometry detected no significant differences in bone mass and microarchitecture in simvastatin treatment group, as well as bone formatin/resorption parameters. These results indicate that simvastatin had no positive effect or impact on bone in rats administered with high dose simvastatin (20 mg/kg/d) for 6 or 9 weeks.


Bone ◽  
1997 ◽  
Vol 20 (5) ◽  
pp. 421-428 ◽  
Author(s):  
J. Verhaeghe ◽  
G. Oloumi ◽  
E. van Herck ◽  
R. van Bree ◽  
J. Dequeker ◽  
...  

2007 ◽  
Vol 48 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Z. F. Sheng ◽  
R. C. Dai ◽  
X. P. Wu ◽  
L. N. Fang ◽  
H. J. Fan ◽  
...  

Background: Bone mineral density (BMD) and microstructural variations have been extensively investigated in recent years; however, the compensation for bone loss between different regions is still unclear. Purpose: To fully characterize regional variations in bone mineral density (BMD) as well as the microstructure and dynamic changes of rat tibial trabeculae that occur with bone loss associated with estrogen deficiency. Material and Methods: Female Sprague-Dawley rats were ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline control). The left tibiae were harvested at baseline, and at postoperative weeks 3 and 15. High-resolution micro-computed tomography (µCT) was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of the rat tibia, specifically the epiphysis and metaphysis. Results: Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels were significantly higher for trabeculae at the epiphysis than metaphysis. Moreover, trabeculae at the epiphysis were thicker, and fewer in number and connectivity than those at the metaphysis, which were more rod like. Trabeculae at the metaphysis were more susceptible to bone loss induced by estrogen deprivation than at the epiphysis, and the regions varied greatly in their adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness were unexpectedly higher at postoperative week 15 than week 3 or baseline. In contrast, at the epiphysis, tissue BMD did not change with time, but trabecular thickness significantly increased at week 15 compared to baseline and was also greater in OVX compared to sham rats. Conclusion: Metaphyseal and epiphyseal trabeculae show regionally specific variations in BMD and microstructure. The former are more susceptible to bone loss induced by estrogen deficiency and would be strengthened by either hypertrophy or hypermineralization, while epiphyseal trabeculae are mainly strengthened by thickening.


2001 ◽  
Vol 86 (11) ◽  
pp. 5273-5276 ◽  
Author(s):  
Mayumi Sato ◽  
Noriyuki Takeda ◽  
Hiroshi Sarui ◽  
Rieko Takami ◽  
Kazuhisa Takami ◽  
...  

Leptin, the product of the ob gene, has been shown to inhibit bone formation in mice. We addressed whether leptin has any role in the regulation of bone mineral density (BMD) in humans. Subjects were 221 adult men with a mean (±sd) age and body mass index of 52.1 ± 8.7 yr and 23.6 ± 2.8 kg/m2. Serum leptin, carboxyterminal propeptide of type 1 procollagen (PICP; a marker of bone formation), and cross-linked carboxyterminal teleopeptide of type 1 collagen (a marker of bone resorption) were measured by RIA. BMD was assessed by single photon absorptiometry, and total fat mass was determined by bioimpedance analysis. BMD was inversely associated with serum leptin concentrations and total fat mass after adjustment for body weight. PICP, but not cross-linked carboxyterminal teleopeptide of type 1 collagen, was inversely correlated with serum leptin. These results may suggest that an increase in serum leptin reduces bone formation and decreases BMD in adult men. Leptin may be a regulator of BMD in humans.


2003 ◽  
Vol 133 (5) ◽  
pp. 1244-1249 ◽  
Author(s):  
Stephanie C. Blum ◽  
Susanne N. Heaton ◽  
Beth M. Bowman ◽  
Maren Hegsted ◽  
Scott C. Miller

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Yanfei L. Ma ◽  
Qing Q. Zeng ◽  
Leah L. Porras ◽  
Anita Harvey ◽  
Terry L. Moore ◽  
...  

We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 μg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xaver Feichtinger ◽  
Patrick Heimel ◽  
Claudia Keibl ◽  
David Hercher ◽  
Jakob Emanuel Schanda ◽  
...  

Abstract Background This study aimed to investigate whether rodent shoulder specimens fixed in formaldehyde for histological and histomorphometric investigations and specimens stained using Lugol’s solution for soft tissue visualization by micro-computed tomography (microCT) are still eligible to be used for bone architecture analysis by microCT. Methods In this controlled laboratory study, 11 male Sprague-Dawley rats were used. After sacrifice and exarticulation both shoulders of healthy rats were assigned into three groups: (A) control group (n = 2); (B) formaldehyde group (n = 4); (C) Lugol group (n = 5). Half of the specimens of groups B and C were placed in a 4% buffered formaldehyde or Lugol’s solution for 24 h, whereas the contralateral sides and all specimens of group A were stored without any additives. MicroCT of both sides performed in all specimens focused on bone mineral density (BMD) and bone microstructure parameters. Results BMD measurements revealed higher values in specimens after placement in Lugol’s solution (p < 0.05). Bone microstructure analyses showed increased BV/TV and Tb.Th values in group C (p < 0.05). Specimens of group C resulted in clearly decreased Tb.Sp values (p < 0.05) in comparison to the control group. Formaldehyde fixation showed minimally altered BMD and bone microstructure measurements without reaching any significance. Conclusions MicroCT scans of bone structures are recommended to be conducted natively and immediately after euthanizing rats. MicroCT scans of formaldehyde-fixed specimens must be performed with caution due to a possible slight shift of absolute values of BMD and bone microstructure. Bone analysis of specimens stained by Lugol’s solution cannot be recommended.


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