Abstract
Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins.
Highlights
Bone is a dynamic tissue that constantly undergoes remodeling by osteoclast-mediated bone resorption and osteoblast-mediated bone formation (Eriksen, 2010; Nakahama, 2010; Raggatt and Partridge, 2010)
We could conclude that galectin-8 derived from osteoblasts can mediate RANKL expression, along with other stimuli that induce RANKL
We provide evidence that an animal lectin of the galectin family regulates osteoclastogenesis and loss of bone mass
Summary
Bone is a dynamic tissue that constantly undergoes remodeling by osteoclast-mediated bone resorption and osteoblast-mediated bone formation (Eriksen, 2010; Nakahama, 2010; Raggatt and Partridge, 2010). Balanced bone remodeling is a hallmark of pathologies such as osteoporosis and cancerous osteolysis (Kozlow and Guise, 2005; Novack and Teitelbaum, 2008; Sturge et al, 2011). Skeletal tissues are composed largely of extracellular matrix (ECM). The ECM of bone contains matricellular proteins that primarily serve as biological modulators. Matricellular proteins interact with cell-surface receptors, such as integrins, the structural matrix, and soluble extracellular factors including growth factors and proteases (Bornstein and Sage, 2002). Through these multiple interactions, matricellular proteins modulate cell function and regulate the availability and activity of proteins sequestered in the matrix. Matricellular proteins contribute to skeletal development, homeostasis, and fracture healing (Alford and Hankenson, 2006)
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