Cited by 42Bone Metabolism and DiseasesBone health and osteoporosis researchBone health and treatments

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

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Zhu, Sheng, Häussling, Victor, Aspera-Werz, Romina H., Chen, Tao, Braun, Bianca, Weng, Weidong, Histing, Tina, Nussler, Andreas K.·2020·International Journal of Molecular Sciences

Abstract

Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.

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Crossref · 10.3390/ijms22010053

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  • Chronic exposure to cigarette smoke extract enhances carbonic anhydrase II and tartrate-resistant acid phosphatase 5b activities in a bone co-culture system, resulting in an osteoporotic microenvironment.

    “Our previous in vitro study revealed that chronic exposure to CSE-enhanced carbonic anhydrate II (CA II, early stage of osteoclastic differentiation [84]) and tartrate-resistant acid phosphatase 5b (TRAP 5b, later stage of osteoclastic differentiation [85]) activities in a bone co-culture system, resulting in an osteoporotic microenvironment [86].”
  • Chronic exposure to cigarette smoke extract enhanced osteoclast function via upregulation of the RANKL/OPG ratio, resulting in an osteoporotic microenvironment, and bisphosphonates can counteract the effects of cigarette smoke extract on the RANKL/OPG pathway.

    “our previous research showed that chronic exposure to CSE enhanced osteoclast function via upregulation of the RANKL/OPG ratio, resulting in an osteoporotic microenvironment, and bisphosphonates can be used to counteract the effects of CSE on the RANKL/OPG pathway [86].”

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Authors
Zhu, S., Häussling, V., Aspera-Werz, R. H., Chen, T., Braun, B., Weng, W., Histing, T., & Nussler, A. K.
Affiliations
BG Klinik Tübingen (DE)
Corresponding author
Nussler, Andreas K.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-12-23
Volume
22
Issue
1
Pages
53
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3116996589
Cited by
42
References
78
Citations by year
2026: 3 · 2025: 8 · 2024: 12 · 2023: 5 · 2022: 5 · 2021: 9
FWCI
1.54
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Eberhard Karls Universität Tübingen
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
bisphosphonates, cigarette smoking, osteoporosis, RANKL/OPG ratio, osteoblasts, osteoclasts, osteoclast activation, cigarette smoke extract, bone homeostasis
MeSH terms
Cell Differentiation, Cell Survival, Diphosphonates, Dose-Response Relationship, Drug, Gene Expression Regulation, Humans, Immunohistochemistry, Osteoblasts, Osteoclasts, Osteoporosis, Smoking, Coculture Techniques, Cell Line, Tumor, Bone Density Conservation Agents, Osteoprotegerin, RANK Ligand

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