Pharmic Activation of PKG2 Alleviates Diabetes-Induced Osteoblast Dysfunction by Suppressing PLCβ1-Ca2+-Mediated Endoplasmic Reticulum Stress

As reported in our previous study, cinaciguat can improve implant osseointegration in type 2 diabetes mellitus (T2DM) rats by reactivating type 2 cGMP-dependent protein kinase (PKG2), but the downstream mechanisms remain unclear. In the present study, we investigated the favorable effect of cinaciguat on primary rat osteoblast, which was cultivated on titanium disc under vitro T2DM conditions (25 mM glucose and 200 μM palmitate), and clarified the therapeutic mechanism by proteomic analysis. The results demonstrated that T2DM medium caused significant downregulation of PKG2 and induced obvious osteoblast dysfunction. And overexpression of PKG2 by lentivirus and cinaciguat could promote cell proliferation, adhesion, and differentiation, leading to decreased osteoblasts injury. Besides, proteomic analysis revealed the interaction between PKG2 and phospholipase Cβ1 (PLCβ1) in the cinaciguat addition group, and we further verified that upregulated PKG2 by cinaciguat could inhibit the activation of PLCβ1, then relieve intracellular calcium overload, and suppress endoplasmic reticulum (ER) stress to ameliorate osteoblast functions under T2DM condition. Collectively, these findings provided the first detailed mechanisms responsible for cinaciguat provided a favorable effect on promoting osseointegration in T2DM and demonstrated a new insight that diabetes mellitus-induced the aberrations in PKG2-PLCβ1-Ca2+-ER stress pathway was one underlying mechanism for poor osseointegration.

Osteoblast Cell Response to LIPSS-Modified Ti-Implants

In the present work, the surface of Ti-6Al-7Nb samples was patterned with Laser Induced Periodic Surface Structures in order to improve biocompatibility, increase tissue ingrowth and decrease bacterial adhesion and inflammatory response for applications in dental and orthopedic implants. Polished and sandblasted disks 10 mm in diameter were treated generating LIPSS under two different sets of parameters. The surface morphology and chemistry were investigated both by secondary electrons imaging, EDS analysis and Atomic Force Microscopy. Primary rat osteoblast culture (passage 2) was used to assess cell toxicity and biocompatibility. Alamar Blue assay was used to access cell viability and proliferation on day 1, 3 and 7. The difference between cell adhesion on polished and sandblasted surface as well as between polished and LIPSS-modified surface are described and discussed.

The Effect of Papaya Seed Ethanol Extract in Vivo on The Number of Osteoblasts Cells of Periodontitis-Induced Rats

The papaya seed ethanol extract is rich in antioxidant ingredients, such as flavonoids and phenolic acids. One of the main factors causing chronic inflammatory in periodontitis is oxidative stress. Administration of papaya seed extract is assumed to increase the number of rat osteoblast cells induced periodontitis. This research was conducted to analyze the effect of papaya seed extract on osteoblasts cells of rat induced periodontitis. This research represented an experimental laboratory-based investigation involving 35 rats of the Rattus norvegicus strain divided into 5 treatment groups (K, P1, P2, P3, P4). Control group (K) was not induced by periodontitis and was not given an extract, while group P induced periodontitis using LPS Phorphyromonas gingivalis (P.gingivalis) for 7 days and continued wire mesh installation around the mandibular incisors in the form of number “8” for 7 days. P1 group was given feed only without extract, while the rest were given extract of 200 mg/kgBB, 300mg/kgBB, and 400mg/kgBB. The data obtained were analyzed with a one-way ANOVA test. The results showed that the average number of osteoblasts varied significantly between the groups. There was an increase in the average number of osteoblast cells in rat induced periodontitis after given papaya seed extract.