Age-related trabecular bone loss is associated with a decline in serum Galectin-1 level

Wenting Xu,Yuxuan Wang,Youjia Xu,Cheng Ni,Guoqing Zheng,Jinshan Zhang

doi:10.1186/s12891-021-04272-y

Abstract

BackgroundSenile osteoporosis with age-related bone loss is diagnosed depending on radiographic changes of bone and bone mineral density (BMD) measurement. However, radiographic alterations are usually signs of medium-late stage osteoporosis. Therefore, biomarkers have been proposed as indicators of bone loss. In the current study, Galectin-1 (Gal-1) showed age-related decline in mice serum. The role of Gal-1 in osteoporosis has not been investigated so far. Hence, the current study illustrated the relationship of serum Gal-1 level with bone loss.MethodsWe employed 6- and 18-month-old mice to establish an animal model of age-related trabecular bone loss, whose bone density and microstructure were investigated by micro-CT. ELISA was used to measure the levels of Gal-1 in serum. The correlation analysis was performed to illustrate the relationship between serum Gal-1 levels and trabecular bone loss. In addition, immunohistochemistry was used to investigate the abundance of Gal-1 in bone marrow of mice. ELISA and western blot were performed to measure the secretion ability and protein expression of Gal-1 in bone marrow stromal cells (BMSC), hematopoietic stem cells (HSC) and myeloid progenitor (MP) respectively. Flow cytometry was used to measure BMSC number in bone marrow. Finally, male volunteers with age-related BMD decrease were recruited and the relationship between serum Gal-1 and BMD was analyzed.ResultsGal-1 showed age-related decline in mice serum. Serum Gal-1 was positively associated with BV/TV of femur, tibia and L1 vertebrae in mice. BMSC secreted more Gal-1 compared with HSC and MP. BMSC number in bone marrow was significantly lower in aged mice compared with young mice. Significant attenuation of Gal-1 protein expression was observed in BMSC and HSC from aged mice compared with young mice. Further, we found a decline in serum Gal-1 levels in men with age-related BMD decrease. There was positive correlation between BMD and serum Gal-1 levels in these men.ConclusionsAge-related trabecular bone loss is associated with a decline in serum Gal-1 level in mice and men. Our study suggested Gal-1 had great potential to be a biomarker for discovering BMSC senescence, diagnosing early osteoporosis and monitoring trabecular bone loss.

Highlights

Bone loss in elderly people, often named as senile osteoporosis, takes place with aging, which leads to bone fragility and increased fractures risk
We found that most of data obtained from Balb/c mouse could be reproduced in C57BL/6 mouse, including trabecular bone loss of femur, tibia and L1 vertebrae in aged mice, age-related decline in Gal-1 levels in serum and bone marrow in aged mice, positive association between Gal-1 levels and trabecular bone volume, and down-regulation of Gal-1 protein expression in bone marrow stromal cells (BMSC) and hematopoietic stem cells (HSC) from aged mice
We found that the age-related trabecular bone loss in C57BL/6 mouse seems more severe than Balb/c mouse demonstrated by micro-CT

Summary

Introduction

Bone loss in elderly people, often named as senile osteoporosis, takes place with aging, which leads to bone fragility and increased fractures risk. It has been one of the most severe diseases affecting the elderly population worldwide [1]. The maintenance of bone homeostasis requires a perfect balance between the destructive activity of osteoclasts and the reparative function of osteoblasts which is called “bone remodeling”. The coupling between these processes presupposes an intimate form of cross-talk between the cells and the existence of autocrine/paracrine mechanisms of interaction [2]. The current study illustrated the relationship of serum Gal-1 level with bone loss

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Conclusion