scholarly journals Silibinin can enhance the osseointegration of titanium rods in ovariectomized rats maintenance treatment with valproic acid

Author(s):  
zhoushan tao

Abstract The present work was aimed to evaluate the effect of valproic acid(VPA),Silibinin (SIM)+VPA on Ti rods osseointegration in ovariectomized rats and further investigation of the possible mechanism. The MC3T3-E1 cells were co-cultured with VPA,SIM +VPA and induced to osteogenesis, and the cell viability,mineralization ability were observed by MTT and ALP staining,Alizarin Red staining and Western blotting. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group OVX and VPA,SIM +VPA, and all the rats received Ti implants and animals belong to group VPA,SIM +VPA received valproic acid(300 mg/kg/day), valproic acid(300 mg/kg/day) plus SIM (25mg/kg/day) , respectively, treatment until death at 12 weeks. Micro-CT, histology, biomechanical testing, bone metabolism index and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results shown that VPA decreased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed combined application of systemic VPA showed harmful effects than OVX group on bone formation in osteopenic rats, with the worse effects on CTX-1, P1NP and microarchitecture as well as biomechanical parameters by down-regulated gene expression of Runx2, OCN, Smad1, BMP-2 and OPG, while up-regulated RANKL. However, after SIM treatment, the above indicators were significantly improved. The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, SIM can reverse the negative effect of VPA on the osseointegration of titanium rods in ovariectomized rats.

2021 ◽  
Author(s):  
Zhoushan Tao ◽  
Tian-Lin Li ◽  
Hong-Guang Xu ◽  
Min Yang

Abstract The purpose was to observe whether Valproic acid (VPA) has a positive effect on bone defect repair via activating Notch signaling pathway in an OVX rat model. The MC3T3-E1 cells were co-cultured with VPA and induced to osteogenesis, and the osteogenic activity was observed by Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining and Western blotting(WB). Then the hydrogel containing VPA was implanted into the femoral epiphysis bone defect model of ovariectomized(OVX) rats for 12 weeks. Micro-CT, Biomechanical testing, histology, Immunofluorescence, RT-qPCR, WB analysis were used to observe the therapeutic effect and explore the possible mechanism. ALP and ARS staining and WB results show that the cell mineralization, osteogenic activity and protein expression of ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, JAG1 of VPA group is significantly higher than the Control group. Micro-CT, Biomechanical testing, histology, Immunofluorescence and RT-qPCR evaluation show that, group VPA presented the stronger effect on bone strength, bone regeneration, bone mineralization, higher expression of VEGFA, BMP-2, ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, JAG1 of VPA when compared with OVX group. Our current study demonstrated that local treatment with VPA could stimulate repair of femoral condyle defects, and these effects may be achieved by activating Notch signaling pathway and acceleration blood vessel and bone formation.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takahiro Naka ◽  
Satoshi Yokose

This study evaluated the application of laser-induced bone therapy (LIBT) to reduce implant healing time in rat tibia. Twenty 10-week-old female Sprague-Dawlay rats were used. The rats received laser irradiation (laser group) or sham operation (control group) on either side of the tibia. Five days after invasion, titanium implants were inserted in proximal tibia. Five, 10, and 20 days after implant placement, tibiae were collected. After taking micro-CT and performing a torque test, the tibiae were decalcified and 8-μm-thick sections were prepared. Specimens were stained with hematoxylin and eosin.Results. Micro-CT images, removal torque values, and histomorphometric analysis data demonstrated a significantly accelerated bone formation in the laser group earlier in the healing process.Conclusion. The use of laser irradiation was effective in promoting bone formation and acquiring osseointegration of titanium implants inserted in rat tibia. LIBT may be suitable for use in implant therapy.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Siddhartha Das ◽  
Kanchan Dholam ◽  
Sandeep Gurav ◽  
Kiran Bendale ◽  
Arvind Ingle ◽  
...  

AbstractAnchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Zi-Li Yu ◽  
Bin-Fang Jiao ◽  
Zu-Bing Li

Lysophosphatidic acid (LPA), a bioactive lipid molecule, has recently emerged as physiological and pathophysiological regulator in skeletal biology. Here we evaluate the effects of LPA on bone formation in vivo in murine femoral critical defect model. Primary femoral osteoblasts were isolated and treated with osteogenic induction conditional media supplemented with 20 μM LPA or LPA analogue. Mineralized nodules were visualized by Alizarin Red S staining. Forty-five C57BL/6 mice underwent unilateral osteotomy. The femoral osteotomy gap was filled with porous scaffolds of degradable chitosan/beta-tricalcium phosphate containing PBS, LPA, or LPA analogue. 2, 5, and 10 weeks after surgery, mice were sacrificed and femurs were harvested and prepared for Micro-Computed Tomography (Micro-CT) and histological analysis. Alizarin Red S staining showed that LPA and LPA analogue significantly enhanced the mineral deposition in osteoblasts. Micro-CT 3D reconstruction images and HE staining revealed that significantly more newly formed bone in osteotomy was treated with LPA analogue when compared to control and LPA group, which was verified by histological analysis and biomechanical characterization testing. In summary, our study demonstrated that although LPA promotes mineralized matrix formation in vitro, the locally administrated LPA was not effective in promoting bone formation in vivo. And bone formation was enhanced by LPA analogue, administrated locally in vivo. LPA analogue was a potent stimulating factor for bone formation in vivo due to its excellent stability.


2020 ◽  
Vol 9 (10) ◽  
pp. e7539109092
Author(s):  
Fernanda Costa Yogui ◽  
Ana Cláudia Ervolino-Silva ◽  
Letícia Pitol-Palin ◽  
Juliana Zorzi Coléte ◽  
Jaqueline Suemi Hassumi ◽  
...  

This study aimed to evaluate the systemic effect of strontium ranelate (SR) on peri-implant bone tissue. Thirty-six adult rats were divided into three experimental groups: sham (SHAM), ovariectomized (OVX) and ovariectomized rats treated with strontium ranelate (OVX-Sr). Strontium ranelate (625mg/kg) was administered by oral gavage on a daily basis. The implants were installed on the tibiae. The euthanasia occurred 42 and 60 days after the implants were installed, and the biomechanical (reverse torque); PCR-RT; histological; immunohistochemical; confocal microscopy and histometric analysis were performed. Quantitative data was subjected to statistical tests with significance level set at p<0.05. Significant increase in implant reverse torque in OVX-Sr was observed when compared to OVX. PCR analysis showed an increase in the genetic expression of the proteins responsible for bone formation in OVX-SR. In the histological analysis, SHAM and OVX-Sr showed a higher degree of maturation of peri-implant bone tissue. Ran-Sr presented higher immunolabeling for ALP and OPN proteins when compared to OVX. In the confocal microscopy, OVX-Sr there was good bone neoformation showed by incorporation of Alizarin red fluorochrome. The histometric analysis, bone implant contact (BIC) and neoformed bone area (NBA) presented statistically difference among all groups, and the Ran-Sr presented the highest BIC. Thus, strontium ranelate improves osseointegration and quality of neoformed bone tissue around implants in estrogen deficient rats.


10.1563/799.1 ◽  
2006 ◽  
Vol 32 (5) ◽  
pp. 211-217 ◽  
Author(s):  
Tetsunari Nishikawa ◽  
Kazuya Masuno ◽  
Masahiko Mori ◽  
Yasuhiro Tajime ◽  
Kenji Kakudo ◽  
...  

Abstract It has not been previously possible to observe bone formation in undecalcified sections with titanium implants at high magnification because of the difficulty in sectioning bone together with implants. A method for examining the bone-implant interface in undecalcified sections is described in which implants are left in situ and confocal laser scanning microscopy (CLSM) is used to examine both the implant surface and adjacent bone. Pulsing of animals at different times with the fluorescent dyes calcein and alizarin red permitted assessment of temporal patterns of bone formation by CLSM. Reflectivity of the polished implant surface permitted accurate assessment of the position of the implant relative to labeled bone. The analysis showed that bone first formed as thin processes towards and across the implant surface, followed by further bone formation behind these processes. The interface between calcified bone tissue and the implant surface was characterized by a 10-μm space. The CLSM technique enabled detailed observations of new bone formation at the titanium implant interface.


2021 ◽  
Vol 10 (10) ◽  
pp. 668-676
Author(s):  
Lei Liu ◽  
ZiHao Li ◽  
Siwen Chen ◽  
Haowen Cui ◽  
Xiang Li ◽  
...  

Aims Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy. Methods Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs. Results Overexpression of BRD4 enhanced while inhibition of Brd4 suppressed the osteogenic differentiation of hBMSCs in vitro. Overexpression of Brd4 increased the expression of mitotically associated long non-coding RNA (Mancr). Downregulation of Mancr suppressed the osteoinductive effect of BRD4. In vivo, inhibition of BRD4 by JQ1 significantly attenuated pathological bone formation in the ATP model (p = 0.001). Conclusion BRD4 was found to be upregulated in HO and Brd4-Mancr-Runx2 signalling was involved in the modulation of new bone formation in HO. Cite this article: Bone Joint Res 2021;10(10):668–676.


2021 ◽  
pp. 088532822110276
Author(s):  
Zhou-Shan Tao ◽  
Tian-Lin Li ◽  
Xing-Jing Wu ◽  
Min Yang

Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.


2016 ◽  
Vol 45 (4) ◽  
pp. 492-500 ◽  
Author(s):  
Juyeong Lee ◽  
Bokyung Kim ◽  
Mi-Hwa Park ◽  
Kyung-Ha Choi ◽  
Changsuk Kong ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pei-I Tsai ◽  
Meng-Huang Wu ◽  
Yen-Yao Li ◽  
Tzu-Hung Lin ◽  
Jane S. C. Tsai ◽  
...  

Abstract Background We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. Methods Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. Results Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. Conclusion The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.


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