Abstract
Steroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by the collapse of the femoral head. SONFH occurs due to the overuse of glucocorticoids (GCs) in patients with immune-related diseases. Among various pathogenesis proposed, the mechanism related to impaired blood vessels is gradually becoming the most convincing hypothesis. Bone endothelial cells including bone microvascular endothelial cells (BMECs) and endothelial progenitor cells (EPCs) play a crucial role in the maintenance of vascular homeostasis. Therefore, bone endothelial cells are key regulators in the occurrence and progression of SONFH. Impaired angiogenesis, abnormal apoptosis, thrombosis and fat embolism caused by the dysfunctions of bone endothelial cells are considered to be the pathogenesis of SONFH. In addition, even with high disability rates, SONFH lacks effective therapeutic approach. Icariin (ICA, a flavonoid extracted from Epimedii Herba), pravastatin, and VO-OHpic (a potent inhibitor of PTEN) are candidate reagents to prevent and treat SONFH through improving above pathological processes. However, these reagents are still in the preclinical stage and will not be widely used temporarily. In this case, bone tissue engineering represented by co-transplantation of bone endothelial cells and bone marrow mesenchymal stem cells (BMSCs) may be another feasible therapeutic strategy.
Highlights
Glucocorticoids have been widely used in the treatment of rheumatic diseases, autoimmune diseases and allergic diseases (Yao et al, 2020)
As long ago as 1935, Phemister raised that vascular impairment led to thrombosis and embolism contributing to the progression of avascular necrosis of the femoral head (ANFH) (Phemister, 1935)
Decreased the rate of empty lacunae and increased blood vessels and the angiogenic biomarker CD31 Promoted angiogenesis by up-regulating the expression of CD31, von Willebrand factor (vWF), PDGFB in bone microvascular endothelial cells (BMECs) and activating Akt and reduced the apoptosis of BMECs by upregulating B cell lymphoma-2 (Bcl-2) associated X (Bax) and down-regulating the expression of Bcl-2 Activated AMP-activated protein kinase (AMPK) mediated by liver kinase B1 (LKB1), thereby inhibiting the mammalian target of rapamycin (mTOR) signaling pathway, recovering autophagy of endothelial progenitor cells (EPCs) and protecting them from Dexinduced apoptosis Promoted angiogenesis and suppressed apoptosis through inhibiting mitochondrial pathway and activating nuclear factor erythroid 2-related factor 2 (Nrf2)
Summary
Glucocorticoids have been widely used in the treatment of rheumatic diseases, autoimmune diseases and allergic diseases (Yao et al, 2020). Abnormal apoptosis, thrombosis and fat embolism caused by the dysfunctions of bone endothelial cells are considered to be the pathogenesis of SONFH. Since blood supply is critical to the maintenance of femoral head structure and function, dysfunction of BMECs and inhibited angiogenesis are potential mechanisms for SONFH (Kerachian et al, 2006).
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