Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats

Abstract

Background: Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH). Methods: A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I. Results: Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm 3 vs . 0.0811 mm 3 , P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group. Conclusions: We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.

Laponite intercalated biomimetic multilayer coating prevents glucocorticoids induced orthopedic implant failure

“…Although current results could not confirm that the WNT16 mediate all beneficial effects of LAP, this emerging Wnt ligand is of interest for future studies. On the other hand, Li + and Mg 2+ were reported to have anti-apoptotic effects on GCs induced cell death [ 50 , 51 ]. It might be the reason that LAP could reverse GCs inhibited proliferation of BMSCs.…”

The Role of Flavonoids in the Osteogenic Differentiation of Mesenchymal Stem Cells

“…Flavonoids can increase bone formation in femoral heads by promoting MSCs proliferation and osteogenic differentiation. In methylprednisolone-induced rat ONFH models, the lithium chloride treatment group displayed a higher vessel volume and better trabecular structures as well as more OCN expression compared with methylprednisolone group, MSCs extracted from rats treated with lithium chloride had higher proliferative and osteogenic ability ( Zhang Y. L. et al, 2021 ). Zefeng Yu et al (2016) also demonstrated lithium could enhance angiogenesis and stabilize osteogenic/adipogenic balance in glucocorticoid-induced ONFH rat models by activating the β-catenin pathway.…”