Bone Homeostasis and Gut Microbial-Dependent Signaling Pathways

Abstract

Bone has self-healing and regenerative abilities and contains three types of cells in adults, including osteoblasts and osteocytes from mesenchymal stem cells and osteoclasts from haematopoietic cells in bone marrow. There are two key cell types that play an important role in bone homeostasis: osteoclasts that absorb bone matrix and osteoblasts that synthesise bone matrix. Osteocytes promote the balance of osteoblasts and osteoclasts in bone construction and bone remodeling, and maintain bone homeostasis by ensuring the balance of calcium and phosphorus metabolism [10]. Bone homeostasis is related to cell development and activation as well as mediation of metabolic and immune activities via signaling pathways. Recent research has shown that the BMP/SMADs, Wnt/β-catenin and OPG/RANKL/RANK signaling pathways play primary roles in bone homeostasis [11,12].Although research on the osteal signaling pathway has progressed, understanding of gut microbialdependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial

“…A tenfold increase in fasting plasma TMAO levels was noted following 3 months of oral LC supplementation in healthy older women [12]. Interestingly, TMAO affects bone homeostasis [13]. The decline in plasma TMAO levels was related to a greater reduction in BMD during a weight loss program in overweight and obese participants, suggesting that TMAO might protect against decreases in BMD [14].…”