PPARβ/δ Agonist Alleviates Diabetic Osteoporosis via Regulating M1/M2 Macrophage Polarization

Diabetic osteoporosis is a common complication in diabetic patients, leading to increased fracture risk and impaired bone healing. As a member of the peroxisome proliferator-activated receptor (PPAR) family, PPARβ/δ agonist is suggested as a therapeutic target for the treatment of metabolic syndrome, and has been reported to positively regulate bone turnover by improving osteogenesis. However, its regulatory role in diabetic osteoporosis has not been reported yet. Here, we explored the therapeutic effects and potential mechanisms of PPARβ/δ agonist to the osteoporotic phenotypes of diabetic mice. Our results indicated that the osteoporotic phenotypes could be significantly ameliorated in diabetic mice by the administration of PPARβ/δ agonists. In vitro experiments suggested that PPARβ/δ agonist treatment could alleviate the abnormal increase of osteoclast activity in diabetic mice by rectifying high glucose-mediated macrophage dysfunction instead of directly inhibiting osteoclast differentiation. Mechanistically, Angptl4 may act as a downstream target of PPARβ/δ to regulate macrophage polarization. In conclusion, our study demonstrates the potential of PPARβ/δ agonist as a therapeutic target for the treatment of osteoporosis and immune homeostasis disorder in diabetic patients.

Chondroitin Sulfate Alleviates Diabetic Osteoporosis and Repairs Bone Microstructure via Anti-Oxidation, Anti-Inflammation, and Regulating Bone Metabolism

Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.

Polycytosine RNA-Binding Protein 1 Regulates Osteoblast Function via a Ferroptosis Pathway in Type 2 Diabetic Osteoporosis

In recent years, type 2 diabetic osteoporosis has become a research hotspot for the complications of diabetes, but the specific mechanism of its occurrence and development remain unknown. Ferroptosis caused by iron overload is considered to be one of the important cause of type 2 diabetic osteoporosis. Polycytosine RNA-binding protein 1 (PCBP1), an iron ion chaperone, was considered as a protector of ferroptosis. The present study aimed to investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes. Firstly, a Cell Counting Kit-8 assay was used to detect the changes of osteoblast viability under the influence of high glucose (HG) and/or ferroptosis inhibitor given at different concentrations and at different times. In addition, the morphological changes of mitochondria in osteoblasts under high glucose were examined via transmission electron microscopy, and the expression levels of PCBP1, ferritin and the ferroptosis-related protein glutathione peroxidase 4 (GPX4) under the action of high glucose were detected via western blotting. Furthermore, a lentivirus was used to silence and overexpress PCBP1. Western blotting was used to detect the expression of levels of the osteoblast functional proteins osteoprotegerin (OPG) and osteocalcin (OCN), while flow cytometry was used to detect the changes of reactive oxygen species (ROS) levels in each group. Under the action of high glucose, the viability of osteoblasts was significantly decreased and the number of mitochondria undergoing atrophy was significantly increased, PCBP1 and ferritin expression levels were increased and GPX4 expression was decreased. Western blotting results demonstrated that infection of the lentivirus overexpressing PCBP1, increased the expression levels of ferritin, GPX4, OPG and OCN, compared with the high glucose group. The flow cytometry results identified a reduction in ROS, and an opposite result was obtained after silencing PCBP1. In conclusion, it was suggested that PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a high glucose environment. Moreover, it was indicated that PCBP1 may be a potential therapeutic target for treating type 2 diabetic osteoporosis.

Effects and Mechanism of Zishen Jiangtang Pill on Diabetic Osteoporosis Rats Based on Proteomic Analysis

Context. Zishen Jiangtang Pill (ZJP) is a Chinese herbal compound, which has a positive therapeutic effect on diabetic osteoporosis (DOP) by regulating glucose metabolism and bone metabolism. However, its regulatory role and mechanism are still unclear. Objective. To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. Materials and Methods. After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). Results. Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. Conclusion. ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP.

Radix Dipsaci extract protects against Rosiglitazone induced bone loss

The dried root of Dipsacus asperoides is known as Radix Dipsaci extract(RDE). It's a kidney-toning herbal medication with a lengthy track record of safe usage in the treatment of bone fractures and joint disorders. The drug rosiglitazone (RSG) causes an imbalance in bone remodelling, which results in increased apoptotic death of osteogenic cells and decreased bone production. The goal of this study was to investigate the effects of RDE on RSGinduced bone loss in diabetic rats in a systematic way. Five groups of six Wistar albino rats were studied: control (vehicle therapy), Streptozotocin (diabetes) group, RDE group, Rosiglitazone, and Rosiglitazone +RDE group. Insulin, oxidative stress, and bone turnover markers in the blood were all detected using ELISA tests. When compared to diabetic control rats, RDE therapy significantly raised insulin and osteocalcin levels. RDE may be able to prevent diabetic osteoporosis by boosting osteogenesis and lowering oxidative stress in the bone.These findings support the use of RDE as a bone loss inhibiting in diabetics. Well-designed clinical trials are likely to yield further scientific evidence on its bone-protective effects and safety. Keywords: Radix Dipsaci, Diabetic osteoporosis, Rosiglitazone.

Rhizoma Drynariae protects against Canaglifloxacin induced bone loss

Osteoporosis is a condition marked by a loss of bone mass and degradation of the bone microstructure, both of which lead to increased fragility and consequent fragility fractures, particularly in the elderly. Rhizoma Drynariae (DRE) is one of the most often used herbal remedies for osteoporosis therapy. Transdermal drug administration is a well- established new method for drug delivery that offers numerous benefits over conventional routes. Wistar albino rats were split into five groups of six rats each: vehicle control, diabeticgroup, DRE group, Canagliflozin (CGF), and CGF + DRE group. Each medication was given by gastric gavage once a day for 35 days. The drug canagliflozin appears to raise the risk of fractur. When compared to the control group, DRE treatment increased bone strength at the femoral diaphysis in osteoporotic fractures in rats by increasing ultimate load and stiffness. The goal of this study is to investigate the anti-osteoporosis effects of DRE in diabetic rats co-treated with CGF. Blood glucose levels and bone mineral density (BMD) were measured. According to the data, DRE produced a significant increase in bone amount. DRE may help prevent and cure diabetic osteoporosis by increasing bone mineral density, according to one study. Keywords: Rhizoma Drynariae Diabetic osteoporosis, Streptozotocin induced diabetes, Canagliflozin