Osteonecrosis of the Femoral Head

Lei

2020

J Orthop Surg Res

Background: It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear. Methods: The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined.Results: MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3.Conclusion: MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.

Section: Discussionmentioning

confidence: 99%

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Lei

2020

J Orthop Surg Res

“…Glucocorticoids are often used to treat diseases such as severe acute respiratory syndrome, organ transplantation, acute lymphoblastic leukemia, multiple myeloma, rheumatoid arthritis, and systemic lupus erythematosus [1][2][3][4][5]. Overdose usage of glucocorticoids is a proven cause of ONFH [6]. The ONFH is a disabling condition and often occurs in individuals between 20 and 50 years old [7].…”

Section: Introductionmentioning

confidence: 99%

Decreased angiogenic and increased apoptotic activities of bone microvascular endothelial cells in patients with glucocorticoid-induced osteonecrosis of the femoral head

BMC Musculoskelet Disord

Zuo

et al. 2020

Background: Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is closely associated with the dysfunction of the bone microvascular endothelial cells (BMECs). The present study investigated the angiogenic and apoptotic activity of the BMECs in glucocorticoid-induced ONFH. Methods: This study enrolled a total of 12 patients, six of whom were assigned to the ONFH group whereas the other six served as the control group. The ONFH group was composed of patients with glucocorticoid-induced ONFH while the control group had femoral neck fractures. BMECs were isolated from the subchondral region of the femoral head. Cell proliferation, cell viability, tube formation assay, Transwell assay, TUNEL assay, and Western blot analysis were performed.Results: BMECs of the two groups were successfully isolated and identified. No significant differences were noticed in BMECs proliferation between the two groups. However, compared to the control, cell viability, tube formation, and migration of BMECs were significantly decreased and the number of TUNEL positive cells was markedly increased in the ONFH group. In the ONFH group, it was also noted that the amount of Bax and cleaved-caspase3 was elevated while that of Bcl-2 was reduced. Conclusion:The findings of our study revealed that BMECs obtained from the glucocorticoid-induced ONFH patients had decreased angiogenic and increased apoptotic activities, which could explain the pathogenesis and progression of glucocorticoid-induced ONFH.

“…Osteonecrosis of the femoral head (ONFH) is a devastating disease which largely advances to femoral head collapse as the natural history and finally necessitates total hip arthroplasty . Although the exact pathogenesis of non‐traumatic ONFH has not been fully elucidated, several risk factors have been identified, including corticosteroids medication, alcohol consumption and several autoimmune diseases . Actually, alcoholism is one of the leading risk factors for ONFH worldwide, and epidemiologic studies indicated that 20%‐45% of ONFH patients were due to alcohol overuse …”

Section: Introductionmentioning

confidence: 99%

Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol‐induced osteonecrosis of the femoral head

Zhu

J Cellular Molecular Medi

et al. 2020

Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol‐induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/β‐catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well‐constructed rat model of ethanol‐induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro‐CT scanning, haematoxylin‐eosin staining, TdT‐mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol‐induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.