The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

Durão, Sara; Gomes, Pedro S.; Colaço, Bruno; Silva, J. C.; Fonseca, Hélder; Duarte, José Alberto; Felino, António; Fernandes, Maria Helena

doi:10.1007/s00198-014-2656-y

Cited by 36 publications

(31 citation statements)

References 38 publications

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“…The ovariectomized rat model is a widely used model to evaluate the efficacy of new drug entities to prevent or treat postmenopausal osteoporosis. Surgical ovariectomy results in a state of high bone turnover and rapid bone loss, which have many similarities between the phenotypes observed in OVX rats and humans [20]. Here, we found that ovariectomy significantly increased serum ALP and OCN, as well as serum CTX and urinary HOP compared with the sham rats.…”

Section: Discussionsupporting

confidence: 59%

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Zhang

Wang²,

Ding³

et al. 2016

Cell Physiol Biochem

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Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

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Section: Discussionsupporting

confidence: 59%

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Zhang

Wang²,

Ding³

et al. 2016

Cell Physiol Biochem

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“…25 After 12 weeks, imperatorin (Solarbio) or normal saline (NS) was administered. Thirty 3-month-old SD male rats were procured from Shanghai Laboratory Animal Center (Shanghai, China).…”

Section: Experimental Animals and Treatmentmentioning

confidence: 99%

“…After 1 week of adaptation, ten rats were subject to sham operation and the remaining rats underwent bilateral ovariectomy (OVX) as per protocol previously reported. 25 After 12 weeks, imperatorin (Solarbio) or normal saline (NS) was administered. Further, the rats were divided into three groups (N = 10/group): SHAM group which underwent sham operation received NS (50 mL/kg/d) by gavage; OVX group which underwent bilateral ovariectomy also received (50 mL/kg/d) NS by gavage; whereas, the other ovariectomy group, IMP received imperatorin (20 mg/kg/d) by gavage.…”

Section: Experimental Animals and Treatmentmentioning

confidence: 99%

Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

Yan

Tang

Chen

et al. 2019

J Cellular Molecular Medi

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Osteoporosis is caused by disturbance in the dynamic balance of bone remodelling, a physiological process, vital for maintenance of healthy bone tissue in adult humans. In this process, a new bone is formed by osteoblasts and the pre‐existing bone matrix is resorbed by osteoclasts. Imperatorin, a widely available and inexpensive plant extract with antioxidative and apoptotic effects, is reported to treat osteoporosis. However, the underlying mechanism and specific effects on bone metabolism have not been elucidated. In this study, we used rat bone marrow‐derived mesenchymal stem cells and found that imperatorin can activate RUNX2, COL1A1 and osteocalcin by promoting the Ser9 phosphorylation of GSK3β and entry of β‐catenin into the nucleus. Imperatorin also enhanced the production of phospho‐AKT (Ser473), an upstream factor that promotes the Ser9 phosphorylation of GSK3β. We used ipatasertib, a pan‐AKT inhibitor, to inhibit the osteogenic effect of imperatorin, and found that imperatorin promotes osteogenesis via AKT/GSK3β/β‐catenin pathway. Next, we used rat bone marrow‐derived monocytes, to check whether imperatorin inhibits osteoclast differentiation via AKT/GSK3β/β‐catenin pathway. Further, we removed the bilateral ovaries of rats to establish an osteoporotic model. Intragastric administration of imperatorin promoted osteogenesis and inhibited osteoclast in vivo. Our experiments showed that imperatorin is a potential drug for osteoporosis treatment.

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“…To date, few biomaterials have been investigated in the repair of OP calvarial defects. For instance, Lin and coworkers found enhanced OP bone regeneration by strontium-substituted calcium silicate bioactive ceramics [18]; another report from Durão and colleagues showed that the implantation of a biocompatible Bovine-Bone Mineral (BBM) graft could heal critical-size calvarial defects in ovariectomized (OVX) rats [19]. However, it was unknown whether ASCs could contribute to the repair of critical-size OP calvarial defects.…”

Section: Introductionmentioning

confidence: 99%

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

Pei

McConda

et al. 2015

Bone

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Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly (lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici’s collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats.

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The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

Abstract: Due to the similarities between the osteoporotic animal model and the human condition of postmenopausal osteoporosis, it might be relevant to consider the potential clinical implication of the osteoporotic condition in the biomaterial-mediated bone tissue healing/regeneration process.

Cited by 36 publications

References 38 publications

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

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