Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model
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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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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].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [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].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [86]
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Self-citationThe role and mechanism of magnetic hydrogels in bone diseases
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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.
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-12-23
- Volume
- 22
- Issue
- 1
- Pages
- 53
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7793101
- 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
- gold
- doi.org
- Licence
- 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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