The Role of Galectin-3 in 1α,25(OH)2D3-Regulated Osteoclast Formation from White Leghorn Chickens In Vitro.

Jianhong Gu,Jianchun Bian,Yutian Zhao,Xuezhong Liu,Wenyan Min,Yan Yuan,Xishuai Tong,Zongping Liu,Xueqing Zhang

doi:10.3390/vetsci8100234

Abstract

Bones play an important role in maintaining the level of calcium in blood. They provide support for soft tissues and hematopoiesis and undergo continuous renewal throughout life. In addition, vitamin D is involved in regulating bone and calcium homeostasis. Galectin-3 (Gal-3) is a β-galactoside-binding protein that can regulate bone cell differentiation and function. Here, we aimed to study the regulatory effects of Gal-3 on vitamin-D-regulated osteoclastogenesis and bone resorption in chicken. Gal-3 expression in bone marrow stromal cells (BMSCs) from 18-day-old chicken embryos was inhibited or overexpressed. BMSCs were then co-cultured with bone marrow monocytes/macrophages (BMMs) with or without addition of 1α,25(OH)2D3. The results showed that 1α,25(OH)2D3 upregulated the expression of Gal-3 mRNA and receptor activator of nuclear-factor κB ligand (RANKL) expression in BMSCs and promoted osteoclastogenesis, as shown by the upregulated expression of osteoclast (OC) markers (CtsK, CAII, MMP-9, and TRAP) and increased bone resorption, a method for measuring the bone resorption area in vitro. Knockdown of Gal-3 by small-interfering RNA (siRNA) in BMSCs downregulated the expression of RANKL mRNA and attenuated the effects of 1α,25(OH)2D3 on osteoclastogenesis and bone resorption. Conversely, overexpression of Gal-3 in BMSCs enhanced the effects of osteoclastogenesis and bone resorption by increasing the expression of RANKL mRNA. These results demonstrated that Gal-3 mediates the differentiation and bone resorption of osteoclasts regulated by 1α,25(OH)2D3.

Highlights

The amount of Tartrate-resistant Acid Phosphatase (TRAP); the expression of cathepsin K (CtsK), TRAP, matrix metalloproteinase-9 (MMP-9), and carbonic anhydrase II (CAII) mRNA; and the area of bone resorption were significantly (p < 0.01 or p < 0.05) increased in the EGFP-Gal-3 group (Figure 5B–F). These results indicate that overexpression of Gal-3 in bone marrow stromal cells (BMSCs) could upregulate osteoclastogenesis and bone resorption
Bone homeostasis homeostasisdepends dependson onbone boneresorption resorptionininmammals mammals and poultry; otherwise, Bone and poultry; otherwise, it it will lead to bone metabolism disorders
BMSCs are the progenitors of various cells

Summary

Introduction

Bone homeostasis is achieved by osteogenesis and bone resorption, which are regulated by osteoblasts (OBs) and osteoclasts (OCs), respectively [1,2]. OCs are responsible for physiological and pathological bone resorption. Excessive increase or decrease in their quantity and activity is detrimental to bone and calcium (Ca) homeostasis [3,4]. Vitamin D is a sterol derivative and has long been considered to promote osteogenesis by promoting the intestinal transport of Ca and osteolysis, ensuring the stability of serum calcium homeostasis.

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