Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model

Zhu, Shaihong; Häussling, Victor; Aspera-Werz, Romina H.; Chen, Tao; Braun, Bianca; Weng, Weidong; Histing, Tina; Nüssler, Andreas K.

doi:10.3390/ijms22010053

Cited by 27 publications

(22 citation statements)

References 77 publications

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“…TRAP 5b activity as a marker of osteoclast activity was measured in culture supernatants as previously described [30,31]. Culture supernatant (30 µL) was transferred to a new cell culture plate with 90 μL of TRAP 5b activity assay solution (0.2% w/v 4-nitrophenyl phosphate, 100 mM sodium…”

Section: Tartrate-resistant Acid Phosphatase (Trap) 5b Activitymentioning

confidence: 99%

“…Bright-field images of the stained cells were captured by microscopy (EVOS FL, Thermo Fisher Scientific). For quantitative measurement, the bound Alizarin Red was dissolved with 10% w/v cetylpyridinium chloride solution and quantified photometrically (λ = 562 nm; Omega plate reader) as described previously [31].…”

Section: Alizarin Red Stainingmentioning

confidence: 99%

“…6e). Matrix mineralization, a marker of functionality and differentiation in osteoblasts [31], was assessed by Alizarin Red staining after 14 days of culture (Fig. 6f).…”

Section: Ds-ecm Supports Osteoclast Differentiation and Matrix Mineralization More Efficiently Than Cap Coatingmentioning

confidence: 99%

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A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation

Weng

Zanetti

Bovard

et al. 2021

J Mater Sci: Mater Med

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The extracellular matrix regulates cell survival, proliferation, and differentiation. In vitro two-dimensional cell experiments are typically performed on a plastic plate or a substrate of a single extracellular matrix constituent such as collagen or calcium phosphate. As these approaches do not include extracellular matrix proteins or growth factors, they fail to mimic a complex cell microenvironment. The cell-derived matrix is an alternative platform for better representing the in vivo microenvironment in vitro. Standard decellularization of a cell-derived matrix is achieved by combining chemical and physical methods. In this study, we compared the decellularization efficacy of several methods: ammonium hydroxide, sodium dodecyl sulfate (SDS), or Triton X-100 with cold or heat treatment on a matrix of Saos-2 cells. We found that the protocols containing SDS were cytotoxic during recellularization. Heat treatment at 47 °C was not cytotoxic, removed cellular constituents, inactivated alkaline phosphatase activity, and maintained the levels of calcium deposition. Subsequently, we investigated the differentiation efficiency of a direct bone coculture system in the established decellularized Saos-2 matrix, an inorganic matrix of calcium phosphate, and a plastic plate as a control. We found that the decellularized Saos-2 cell matrix obtained by heat treatment at 47 °C enhanced osteoclast differentiation and matrix mineralization better than the inorganic matrix and the control. This simple and low-cost method allows us to create a Saos-2 decellularized matrix that can be used as an in vivo-like support for the growth and differentiation of bone cells.

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Section: Tartrate-resistant Acid Phosphatase (Trap) 5b Activitymentioning

confidence: 99%

Section: Alizarin Red Stainingmentioning

confidence: 99%

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A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation

Weng

Zanetti

Bovard

et al. 2021

J Mater Sci: Mater Med

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“…Additionally, nutritional support, especially an adequate intake of vitamin D and calcium, constitutes an essential element of the therapy [20]. In turn, bisphosphonates are common anti-osteoclastic drugs, but they also reduce cigarette smoking-induced osteoporotic alterations of osteoblasts and osteoclasts [21].…”

Section: Introductionmentioning

confidence: 99%

“…According to Zhu et al, bisphosphonates may be drugs for osteoporotic patients, especially smokers [21]. Many studies showed that bisphosphonates increase OPG expression and inhibit the expression of RANKL, which is opposed to the impact of nicotine on OPG/RANKL/RANK pathway [31,32].…”

Section: Introductionmentioning

confidence: 99%

Impact of Cigarette Smoking on the Risk of Osteoporosis in Inflammatory Bowel Diseases

Ratajczak

Szymczak-Tomczak

Rychter

et al. 2021

JCM

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Cigarette smoking constitutes one of the most important modifiable factors of osteoporosis, as well as contributes to an early death, tumors, and numerous chronic diseases. The group with an increased risk of a lower bone mineral density are patients suffering from inflammatory bowel diseases. In fact, tobacco smoke, which contains more than 7000 chemical compounds, affects bone mineral density (BMD) both directly and indirectly, as it has an impact on the RANK-RANKL-OPG pathway, intestinal microbiota composition, and calcium–phosphate balance. Constant cigarette use interferes with the production of protective mucus and inhibits the repair processes in the intestinal mucus. Nicotine as well as the other compounds of the cigarette smoke are important risk factors of the inflammatory bowel disease and osteoporosis. Additionally, cigarette smoking may decrease BMD in the IBD patients. Interestingly, it affects patients with Crohn’s disease and ulcerative colitis in different ways—on the one hand it protects against ulcerative colitis, whereas on the other it increases the risk of Crohn’s disease development. Nevertheless, all patients should be encouraged to cease smoking in order to decrease the risk of developing other disorders.

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Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening

Chen,

Xin,

Hammour

et al. 2024

Arch Toxicol

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Drug toxicity is an important cause of chronic liver damage, which in the long term can lead to impaired bone homeostasis through an imbalance in the liver-bone axis. For instance, non-steroidal anti-inflammatory drugs (e.g., diclofenac), which are commonly used to control pain during orthopaedic interventions, are known to reduce bone quality and are the most prevalent causes of drug-induced liver damage. Therefore, we used human cell lines to produce a stable, reproducible, and reliable in vitro liver-bone co-culture model, which mimics the impaired bone homeostasis seen after diclofenac intake in vivo. To provide the best cell culture conditions for the two systems, we tested the effects of supplements contained in liver and bone cell culture medium on liver and bone cell lines, respectively. Additionally, different ratios of culture medium combinations on bone cell scaffolds and liver spheroids’ viability and function were also analysed. Then, liver spheroids and bone scaffolds were daily exposed to 3–6 µM diclofenac alone or in co-culture to compare and evaluate its effect on the liver and bone system. Our results demonstrated that a 50:50 liver:bone medium combination maintains the function of liver spheroids and bone scaffolds for up to 21 days. Osteoclast-like cell activity was significantly upregulated after chronic exposure to diclofenac only in bone scaffolds co-cultured with liver spheroids. Consequently, the mineral content and stiffness of bone scaffolds treated with diclofenac in co-culture with liver spheroids were significantly reduced. Interestingly, our results show that the increase in osteoclastic activity in the system is not related to the main product of diclofenac metabolism. However, osteoclast activation correlated with the increase in oxidative stress and inflammation associated with chronic diclofenac exposure. In summary, we established a long-term stable liver-bone system that represents the interaction between the two organs, meanwhile, it is also an outstanding model for studying the toxicity of drugs on bone homeostasis.

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Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model

Cited by 27 publications

References 77 publications

A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation

A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation

Impact of Cigarette Smoking on the Risk of Osteoporosis in Inflammatory Bowel Diseases

Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening

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