Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects

Abstract

Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties.

Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity

“…All procedures were approved by the Chang Gung Memorial Hospital review committee (IACUC approval number 2018121701). Ten-week-old male C57BL/6NCrlBltw mice were used for the femoral defect model [ 25 , 26 ].…”

“…A 3D image was constructed using CTVox software (version 3.3.0, SkyScan) for illustration purposes. For the detailed procedure, please refer to our previously published studies [ 25 , 26 ].…”

Knockdown of FOXA1 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the ERK1/2 signalling pathway

“…All mice were divided randomly and evenly into three groups: (1) control group, (2) KD-NC (negative-control group of mBMSCs with FOXA1-KD), and ( 3) KD (mBMSCs with FOXA1-KD) (n = 10 per group). The mouse defect model was constructed as previously reported [49][50][51][52], and the surgical operations were performed by two experienced orthopaedic surgeons. Brie y, mice were anaesthetised by intraperitoneal injection of 0.3% pentobarbital sodium (30 mg/kg body weight).…”

Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns

“…For instance, mesenchymal stem cells stimulated by LTA from S. aureus upregulate the expression of various osteogenic markers, such as Runx2, alkaline phosphatase (ALP), type I collagen, and calcium deposition through enhanced autophagy [ 39 ]. Additionally, LTA from S. aureus promotes the synthesis of bone bridge, ossification, and healing of femoral fractures induced by medial parapatellar arthrotomy [ 40 ]. It is likely that such phenomenon was induced by enhancing osteoblast differentiation and inhibiting osteoclast activation [ 40 ].…”

“…Additionally, LTA from S. aureus promotes the synthesis of bone bridge, ossification, and healing of femoral fractures induced by medial parapatellar arthrotomy [ 40 ]. It is likely that such phenomenon was induced by enhancing osteoblast differentiation and inhibiting osteoclast activation [ 40 ]. Although LTA appears to be a potential treatment for bone diseases, further studies are needed because LTA causes differential immune responses depending on the source of bacteria.…”