Circulating microRNAs Related to Bone Metabolism in HIV-Associated Bone Loss.

Maria P Yavropoulou,Alexandros Tzallas,Polyzois Makras,Maria Pikilidou,Sideris Nanoudis,Simeon Metallidis,Georgios Ntritsos,Dimitrios Chatzidimitriou,Olga Tsachouridou,Artemis Kolynou,Olga Tsave,Dimitrios G Tsalikakis,Lemonia Skoura

doi:10.3390/biomedicines9040443

Abstract

The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP−) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV−), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower (p < 0.001) while the expression of miRNA-24-2-5p was significantly higher (p = 0.030) in HIV+/OP+ compared to HIV+/OP−. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.

Highlights

The prevalence of osteopenia and osteoporosis is greatly increased in individuals with human immunodeficiency virus (HIV+) of all ages compared to the general population [1,2], reaching up to 67% and 15%, respectively
In order to determine whether HIV-associated bone loss is associated with and can be predicted by certain alterations in the expression of bone-related miRNAs in serum, we investigated the expression profile of circulating miRNAs that are linked to bone metabolism in male HIV+ individuals with osteoporosis
Serum levels of the measured bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP), and beta-CTX, did not differ significantly between groups, they tended to be higher in HIV+ compared to HIV− individuals (Table 2)

Summary

Introduction

The prevalence of osteopenia and osteoporosis is greatly increased in individuals with human immunodeficiency virus (HIV+) of all ages compared to the general population [1,2], reaching up to 67% and 15%, respectively. HIV+ individuals experience a higher low-trauma fracture risk, ranging from 1.6 to 3-fold, compared to the general population, especially after initiation of highly active antiretroviral therapy (HAART) [3,4]. In addition to traditional osteoporotic risk factors, direct effects of HIV-1 viral proteins and inflammatory cytokines on bone cells as well as the need for long-term. As HIV-associated bone loss is associated with increased osteoclastic activity, the impact of the impaired immune system response [7,8] and the effect of increased proinflammatory cytokines in osteoclastogenesis [9] have been thoroughly studied. It has been suggested that a direct effect of viral proteins in osteoclasts plays a key role in the increased osteoclastic activity seen in HIV-associated bone loss. A recent experimental study demonstrated the presence of HIV-infection in osteoclasts of HIV-1-infected humanized mice and of human synovial explants exposed to the HIV-1 virus showing that, at the cellular level, the negative factor (NEF) gene viral protein has an essential role in osteoclast number and function [10]

Methods

Results

Conclusion