The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

Abstract

Background: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Methods: Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. Results: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Conclusion: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

Diminished membrane recruitment of Akt is instrumental in alcohol‐associated osteopenia via the PTEN/Akt/GSK‐3β/β‐catenin axis

“…The relative expression of the genes was normalized to b-actin expression. The RT-PCR was carried out as described previously [55]. Primer sequences: PTEN, forward:5 0 -TTT TGA AGA CCA TAA CCC AC-3 0 and reverse 5 0 -TAT CAT TAC ACC AGT TCG TC-3 0 , LncRNA PTENP1, forward:5 0 -TTG TAG TTG TGA TGG AAG TTT GAA T-3 0 and reverse:5 0 -CCA CCC CCA CAA ATA CTC ACA-3 0 , b-actin, forward:5 0 AAG GTG ACA GCA GTC GGT T-3 0 and reverse:5 0 -TGT GTG GAC TTG GGA GAG G-3 0 .…”

“…The sample absorption at 450 nm was analyzed, and a standard curve was generated for each protein. The NE-PER Nuclear and Cytoplasmic Extraction Reagents kit (Pierce Biotechnology, Rockford, IL, USA) was used for nuclear and cytosolic extract preparation as described previously [55].…”

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

“…A five-year follow-up study revealed that the combination of implantation of autologous bone marrow cells and auto-iliac cancellous bone grafts generated comparable clinical results with those of head-preserving procedures in medium-sized lesions [16], indicating that BMSCs implantation is promising for ONFH treatment. The findings of a previous investigation demonstrated that the Akt activator and cordycepin promoted BMSC-induced osteogenesis [17, 18]. Furthermore, P-glycoprotein (P-gp) overexpression was found to decrease the risk of steroid-induced ONFH [19].…”

Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

“…It has been demonstrated that in osteoporosis, BMSCs favour adipogenesis over osteogenesis [2][3][4]. Thus, uncovering the complex regulation pathways of normal BMSC differentiation and restoring the decreased osteogenic differentiation of BMSCs is a promising therapeutic strategy for osteoporosis.…”