Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in mice and humans. However, a potential involvement of other PPAR subtypes in the regulation of bone homeostasis has remained elusive. Here we report a previously unrecognized role of PPARβ/δ as a key regulator of bone turnover and the crosstalk between osteoblasts and osteoclasts. In contrast to activation of PPARγ, activation of PPARβ/δ amplified Wnt-dependent and β-catenin-dependent signaling and gene expression in osteoblasts, resulting in increased expression of osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis. Accordingly, PPARβ/δ-deficient mice had lower Wnt signaling activity, lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia. Pharmacological activation of PPARβ/δ in a mouse model of postmenopausal osteoporosis led to normalization of the altered ratio of tumor necrosis factor superfamily, member 11 (RANKL, also called TNFSF11) to OPG, a rebalancing of bone turnover and the restoration of normal bone density. Our findings identify PPARβ/δ as a promising target for an alternative approach in the treatment of osteoporosis and related diseases.
Oxygen is a fundamental requirement for cellular metabolism. Hypoxia is a state of oxygen deprivation of the tissues. Cells develop numerous adaptive mechanisms to survive hypoxic insult.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.
The treatment of large bone defects remains challenging due to the lack of spatiotemporal management of the immune microenvironment, inflammation response and bone remodeling. To address these issues, we designed and developed a nanoparticle/hydrogel hybrid system that can achieve the combined and sequential delivery of an anti-inflammatory factor (IL-10) and osteogenic drug (icariin, ICA). A photopolymerizable composite hydrogel was prepared by combining gelatin methacryloyl (GelMA) and heparin-based acrylated hyaluronic acid (HA) hydrogels containing IL-10, and poly(dl-lactide-co-glycolide) (PLGA)-HA nanoparticles loaded with ICA were incorporated into the composite hydrogels.
Injectable platelet-rich fibrin (i-PRF) is a novel platelet concentrate that has been employed in dentistry with the objective of promoting tissue regeneration and healing. In contrast to platelet-rich plasma (PRP), i-PRF is more straightforward to handle, more cost-effective, and free from anticoagulants, which reduces biochemical alterations. The i-PRF procedure was developed in 2014 by adjusting the centrifugation forces.
Objective: Aim: The aim of this study is to determine the dynamics of histoarchitectural changes in the bone-ceramic regenerate after transplantation β-tricalcium phosphate into an experimental defect in the rabbit mandible.
Patients And Methods: Materials and Methods: Adult male rabbits aged 6-7 months and weighing 2.5-3 kg were used for the study.
The IncRNA was initially believed to be dispensable for physiology due to the lack of observable phenotypes in knockout (KO) mice. However, our study challenges this conclusion. We found that both KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis.
