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

Abstract

Background Senile 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. Methods We 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. Results Gal-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. Conclusions Age-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.

Galectin‐1 deletion in mice causes bone loss via impaired osteogenic differentiation potential of BMSCs

“…Secondly, Gal‐1 could activate itself expression through β‐catenin, that is, there was positive feedback regulation via Wnt/β‐catenin signaling to maintain Gal‐1 high‐level expression during osteogenic differentiation of BMSCs. Finally, in addition to the observation of the decrease in BMSCs number in aged mice, 21 it was observed that the osteogenic differentiation potential became attenuated in BMSCs from aged mice compared with young mice in the current study.…”

“…BMSCs secret high-level Gal-1. 21,27 In the current study, the molecular mechanisms underlying Gal-1 expression regulation during osteogenic differentiation of BMSCs were investigated. Firstly, mRNA and protein expression of Gal-1 during osteogenic differentiation of BMSCs was evaluated at week 1, 2, 3, and 4 after osteo-induction.…”

“…A previous study provided evidences that BMSCs secreted high-level Gal-1 and age-related trabecular bone loss was associated with a decline in serum Gal-1 level in both aged mice and patients. 21 In the current study, we also employed the mice model of age-related bone loss to elucidate the molecular mechanisms underlying the association of age-related bone loss with decline in Gal-1 level. Firstly, we found that Gal-1 expression was up-regulated steadily during osteogenic differentiation of BMSCs.…”

“…Andersen et al 20 demonstrated that Gal‐1 inhibited the proliferation of human BMSCs, increased the ALP activity, and inhibited the secretion of Ocn. A previous study demonstrated that age‐related trabecular bone loss was associated with a decline in serum Gal‐1 level in both aged mice and patients 21 . However, the regulation of Gal‐1 expression during BMSCs osteogenic differentiation and the molecular mechanisms underlying the effects of Gal‐1 on BMSCs osteogenic differentiation remain poorly understood so far.…”

N-Glycosylation and Inflammation; the Not-So-Sweet Relation

“…One possibility is autocrine stimulation of proinflammatory macrophages by binding selfexpressed Gal-1 to N-glycan ligands on their surface that normally lack the inhibitory a2,6-linked sialic acid. The Gal-1/ IFN-b feedback loop is thought to occur at the time of termination of acute inflammation, so any misstep (e.g., insufficient Gal-1 expression) could lead to the development of a chronic inflammatory state, as decreased Gal-1 has been observed in several chronic inflammatory states (120)(121)(122).…”