Gut microbiota has emerged as an important regulator of bone homeostasis. In particular, the modulation of innate immunity and bone homeostasis is mediated through the interaction between microbe-associated molecular patterns (MAMPs) and the host pattern recognition receptors including Toll-like receptors and nucleotide-binding oligomerization domains. Pathogenic bacteria such as Porphyromonas gingivalis and Staphylococcus aureus tend to induce bone destruction and cause various inflammatory bone diseases including periodontal diseases, osteomyelitis, and septic arthritis. On the other hand, probiotic bacteria such as Lactobacillus and Bifidobacterium species can prevent bone loss. In addition, bacterial metabolites and various secretory molecules such as short chain fatty acids and cyclic nucleotides can also affect bone homeostasis.
MAMPs |
Receptor |
Effects |
References |
---|---|---|---|
Lipopolysaccharide |
TLR4 |
Inducing bone loss Inhibiting osteoclastogenesis on macrophages Facilitating osteoclast differentiation on committed osteoclasts Downregulating osteoblast differentiation |
|
[ | |||
, |
MAMPs |
Mechanism |
Effects on Bone Metabolism |
References |
||
---|---|---|---|---|---|
Short chain fatty acids |
Activation of GPCRs Inhibition of histone deacetylases |
Inhibited osteoclast differentiation and function Upregulated osteogenic factors in low dose Attenuated osteoblast differentiation and mineralization Prevented bone loss in various mouse models |
[109,111,112,114][60][61][6232,33,][31][32][34,35][28][29]][63]33][34][35] |
||
Lipoteichoic acid |
] | ||||
Extracellular vesicles |
TLR2 |
Activation of TLR2 Induction of pro-inflammatory cytokines Healing femoral fractures in mice Attenuating osteoclast differentiation and activating phagocytosis Upregulating osteogenic markers and osteoblastogenesis |
[40] |
||
Downregulated osteoblast differentiation and activity Regulated RANKL and OPG expression in mesenchymal cells |
Lipoprotein |
||||
Extracellular polysaccharides |
TLR2 |
Activation of TLR2 Promoting bone resorption Upregulating osteoclast differentiation Stimulating osteoblasts to elevate RANKL/OPG ratio |
Inhibited osteoclast differentiation from macrophages, but some EPS increased collagenolytic activity of osteoclasts |
||
Enhanced osteoblast differentiation, but oral pathogen-derived CPS decreased proliferation of osteoblasts |
Fimbria |
||||
Cyclic dinucleotides |
TLR4 |
Induction of STING-mediated IFN-β Inducing osteoclastogenesis and bone resorption |
Inhibited differentiation of macropahges into mature osteoclasts Alleviated RANKL-induced bone destruction |
||
Peptidoglycan |
NOD1 |
Enhancing osteoclastogenesis and bone resorption Triggering osteoclast differentiation synergistically with LPS |
|||
NOD2 |
Upregulation of bone density Facilitating osteoblast differentiation Diminishing osteoclastogenesis by reducing RANKL/OPG ratio |