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

Abstract

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.

IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

“…Except for TAZ expression, the upregulation of RUNX2 and OCN expression in the IRS-1 overexpression group also suggested that IRS-1 could enhance the RUNX2- and OCN-driven osteogenic gene expression accordingly. At first, we discovered that IRS-1 and RUNX2 mRNA levels were increased at the early stage of osteogenesis, while the OCN mRNA levels presented a delayed increase, as shown in previous studies (Born et al, 2012; Zhang et al, 2016). In addition, the mRNA and protein levels of RUNX2 and OCN were both significantly increased after 3 days' induction of the osteogenic medium in the IRS-1 overexpression group.…”

Effect of Chlorella Pyrenoidosa Protein Hydrolysate-Calcium Chelate on Calcium Absorption Metabolism and Gut Microbiota Composition in Low-Calcium Diet-Fed Rats

“…ALP play an important role in the process of bone calcification; it will increase when calcification is abnormal [64]. High serum ALP level may interfere with calcium absorption [65,66,67,68]. The results illustrated that the high dose of CPPH-Ca treatment could restore calcification to a normal level, and that calcium in HCPPH-Ca was more easily absorbed, calcified and its effect was better compared with inorganic calcium, even in the HGCa.…”

“…Interestingly, our results illustrated that HCPPH-Ca treatment could effectively improve bone index parameters, and more effective absorption and utilization of calcium were found in rats fed HCPPH-Ca compared with inorganic calcium and even HGCa [67]. BMD and BMC are the gold standards for the evaluation of low-calcium deficiency risk [66]. In addition, the BMD of femur and tibia were markedly reduced in the model and HCaCO 3 groups compared with the HCPs-Ca, HGCa and control groups.…”

Pharmacological activation of TAZ enhances osteogenic differentiation and bone formation of adipose-derived stem cells

“…Given the critical roles of TAZ underlying osteogenic differentiation of MSCs from diverse sources, it is of great interest and importance to translate these findings into therapies for bone repair and regeneration. Local delivery of TAZ by lentivirus alleviated the osteoporotic phenotypes in the femoral neck of ovariectomized rats [ 42 ]. Several research groups have successfully identified several chemical or bioactive compounds such as TM-25659, epicatechin gallate, Phorbaketal A, IBS008738, kaempferol, and ethacridine as TAZ activators that generated the corresponding biological effects mediated by TAZ in diverse cell types [ 23 , 24 , 26 , 40 , 43 , 44 ].…”