Bacterially induced bone destruction: mechanisms and misconceptions

Abstract

Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

A Comparison of Zirconia and Titanium Abutments for Microleakage

“…E. coli LPS was preferred compared with other oral flora-related bacterial LPS as it is easily accessible and it is still relevant for oral cavity. 31 Baseline LPS contamination is a commonly reported problem related to similar in vitro study models as LPS can be easily found in the surrounding environment. Most of the published in vitro studies report several cycles of autoclaving and/or chemical processing to remove this type of baseline LPS prior to the actual experiment.…”

The bacterial gene lfpA influences the potent induction of calcitonin receptor and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive multinucleated giant cells

“…Bacterially induced osteoclastogenesis is not without precedent (see review by Nair et al, 1996). Multinucleation and TRAP production by spleen cells has been reported following treatment with Porphyromonas gingivalis, a periodontal pathogen, or lipopolysaccharide from E. coli (Abu-Amer et al, 1997;Jiang et al, 2002), and the addition of surface-associated material from P. gingivalis, Actinobacillus actinomycetemcomitans, or Staphylococcus aureus to bone marrow cultures reportedly causes multinucleation and bone resorption in vitro (Wilson et al, 1986;Wilson et al, 1993;Nair et al, 1995), although this effect may be due to an increase in RANKL by associated osteoblasts, rather than a direct effect on osteoclast precursors.…”

“…Osteoclast-like cells have been observed following bacterial treatment, albeit after long incubation times (Nair et al, 1996;Abu-Amer et al, 1997). As B. pseudomallei and Burkholderia thailandensis induce MNGC formation, and osteoclasts are MNGCs, we investigated whether any similarity exists between osteoclasts and B. pseudomallei-induced or B. thailandensis-induced MNGCs.…”

Effect of novel curcumin‐encapsulated chitosan–bioglass drug on bone and skin repair after gamma radiation: experimental study on a Wistar rat model

“…15 Over the past decade, there has been considerable evidence that microorganisms may be implicated in bone loss and osteoporosis. 16 For that, during osteoporotic bone grafting, the infection is still one of the most serious complications in implant surgeries. Specifically, Staphylococcus aureus and Brucella are known to infect, survive within human osteoblastic cells and secrete cytokines such as tumour necrosis factor (TNF)-α and interleukin (IL)-1ß.…”