Suppressing phosphoinositide-specific phospholipases Cγ1 promotes mineralization of osteoarthritic subchondral bone osteoblasts via increasing autophagy, thereby ameliorating articular cartilage degeneration

• DOI: 10.1016/j.bone.2021.116262
• Publication Date: 2021-11-21T00:06:36Z
• Authors: Yue Wang; Tongen Zhang; Yang Xu; Rui Chen; Ning Qu; Bing Zhang; Chun Xia
• Keywords: Cartilage, Articular; Mice; 0303 health sciences; 03 medical and health sciences; Osteoblasts; Phospholipases; Autophagy; Animals; Osteoarthritis, Knee; Phosphatidylinositols; Rats

Phosphoinositide-specific phospholipases C-γ1 (PLC-γ1) signaling has been shown to modulate osteoarthritis (OA) chondrocyte metabolism. However, the role of PLC-γ1 in OA osteoblasts remains unclear. Herein, whether and how was involved mineralization subchondral bone were investigated.Primary non-OA human rat isolated from or calvaria cultured vitro, as well mouse pre-osteoblastic cell line MC3T3-E1 cells. Rat knee model induced by anterior cruciate ligament transection (ACLT), which canal carried out surface lateral epicondyle femur using micro-electric drill. Morphological characteristics structure articular cartilage assessed CT, micro-CT, Safranin O/Fast green staining, respectively. Mineralization measured alizarin red staining. The expression production genes osteoblastic phenotype evaluated qPCR, western blotting, immunohistochemistry assays, inhibitions performed inhibitors ShRNAs.The decreased relative density thickness early stage increased one late observed ACLT-rat model. Decreased ALP OCN levels absorbance values ARS content vitro 2 w post-ACLT model, IL-1β-treated (for maintaining mimicking inflammatory status) osteoblasts. Atg7 level LC3BII/I ratio combination with an increase P62 level, concomitant mRNA Specific inhibition ShRNAs inhibitor (U73122) elevated accompanied a decrease Furthermore, promoting effect on reversed endoplasmic reticulum (ER) stress activator HA15, autophagic CQ 3MA. Injection U73122 reduced aberrant formation attenuated degeneration ACLT-rat.Aberrant changes altered mineralization. Impaired autophagy contributed OA. promoted through increasing osteoblasts, partially attributed suppression ER stress. Targeting could be more efficacious for therapy treating at same time. In summary, we hypothesize that suppressing PLCγ1 promotes osteoarthritic via autophagy, thereby ameliorating degeneration.