Abstract

Methylsulfonylmethane (MSM) is a naturally occurring anti-inflammatory compound that effectively treats multiple degenerative diseases such as osteoarthritis and acute pancreatitis. Our previous studies have demonstrated the ability of MSM to differentiate stem cells from human exfoliated deciduous (SHED) teeth into osteoblast-like cells. This study examined the systemic effect of MSM in 36-week-old aging C57BL/6 female mice in vivo by injecting MSM for 13 weeks. Serum analyses showed an increase in expression levels of bone formation markers [osteocalcin (OCN) and procollagen type 1 intact N-terminal propeptide (P1NP)] and a reduction in bone resorption markers [tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collag (CTX-I)] in MSM-injected animals. Micro-computed tomographic images demonstrated an increase in trabecular bone density in mandibles. The trabecular bone density tended to be higher in the femur, although the increase was not significantly different between the MSM- and phosphate-buffered saline (PBS)-injected mice. In mandibles, an increase in bone density with a corresponding decrease in the marrow cavity was observed in the MSM-injected mice. Furthermore, immunohistochemical analyses of the mandibles for the osteoblast-specific marker – OCN, and the mesenchymal stem cell-specific marker – CD105 showed a significant increase and decrease in OCN and CD105 positive cells, respectively. Areas of bone loss were observed in the inter-radicular region of mandibles in control mice. However, this loss was considerably decreased due to stimulation of bone formation in response to MSM injection. In conclusion, our study has demonstrated the ability of MSM to induce osteoblast formation and function in vivo, resulting in increased bone formation in the mandible. Hence, the application of MSM and stem cells of interest may be the right combination in alveolar bone regeneration under periodontal or other related diseases that demonstrate bone loss.

Highlights

  • Bone loss associated with osteoporosis represents a significant health care problem, and it is related to increased activation of osteoclast bone resorption function (Mundy, 2007; Khosla et al, 2012; Soysa and Alles, 2016; Cai et al, 2017)

  • Consistent with the observation shown in stem cells from human exfoliated deciduous (SHED) (Aljohani et al, 2019), MSM increased Alkaline phosphatase (ALP) activity in these cells in the basal growth medium (BM) in vitro

  • This increase was equivalent to an osteogenic medium (OM) containing osteogenic factors (Supplementary Figure 1)

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Summary

Introduction

Bone loss associated with osteoporosis represents a significant health care problem, and it is related to increased activation of osteoclast bone resorption function (Mundy, 2007; Khosla et al, 2012; Soysa and Alles, 2016; Cai et al, 2017). Increased pro-inflammatory markers in older adults represent aging-related osteoporosis (Weitzmann and Pacifici, 2006; Pacifici, 2008). Increased inflammation in aged mammals is correlated with higher circulating pro-inflammatory cytokines than young adults (Abdelmagid et al, 2015). The reason is that increased circulating pro-inflammatory mediators could induce molecular changes in the periodontal tissue and exaggerate bone loss in older adults (Liang et al, 2010). Tooth loss in older adults is linked with periodontal disease (Koduganti et al, 2009)

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