Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study

Xin-Yuan Wang,Hao Wang,Zeng-Xin Jiang,Lin-Jing Gong,Chen-Zhong Wang,Chang Jiang,Kang-Ning Chen,Jun-Ming Huang,Zhe Wang,Zuo-Qin Yan,Tian-Le Ma,Guo-Bin Qi,Zhi-Ying Pang

doi:10.1186/s12944-021-01601-x

Abstract

BackgroundOsteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH.MethodsNineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments.ResultsIn the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes.ConclusionsThe accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Highlights

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders
Quantitative real-time polymerase chain reaction Total RNA was extracted from Murine long-bone osteocyte Y4 (MLO-Y4) or RAW 264.7 cells using Trizol (Invitrogen, Carlsbad, USA) and lowdensity lipoprotein (LDL) and oxidized LDL (ox-LDL) accumulated in the necrotic region, the empty bone lacunae were more likely to accumulate ox-LDL
In vitro studies showed that ox-LDL, but not native LDL, might be responsible for aggravating osteocyte viability and enhancing apoptosis

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Numerous studies have demonstrated that high blood levels of lowdensity lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. Osteonecrosis of the femoral head (ONFH) is a common but intractable orthopaedic disease that mainly affects younger people. Circulating and local lipid metabolic disorders are crucial in ONFH, especially in cases associated with GC or alcohol abuse [3]. The second pathway involves altered levels of circulating lipids, which may form fat microemboli in the microvessels of the femoral head

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