Related Experiment Videos
Proliferative response of different human osteoblast-like cell models to proinflammatory cytokines
M E Harbour1, J W Gregory, H R Jenkins
1Department of Child Health, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Insights
Inflammatory bowel disease increases osteopenia risk in children. Pro-inflammatory cytokines like tumor necrosis factor-alpha and IL-1beta differentially affect osteoblast-like cell proliferation, impacting bone health.
Area of Science:
- Pediatric Bone Biology
- Inflammatory Diseases
- Cellular Physiology
Background:
- Children with inflammatory bowel disease (IBD) face an elevated risk of osteopenia.
- The inflammatory process in IBD, marked by cytokine overproduction, is a suspected contributor to osteopenia development.
Purpose of the Study:
- To investigate the impact of inflammatory cytokines on osteoblast-like cell proliferation.
- To determine if disease activity in IBD contributes to osteopenia through cytokine-mediated effects on bone cells.
Main Methods:
- In vitro assays were conducted using osteoblast-like cells from various sources: pediatric bone explants, bone marrow stromal cells (osteoprogenitors), MG-63 osteosarcoma cells, and HCC1 (transformed osteoprogenitors).
- Cells were exposed to tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) to assess proliferation responses.
Main Results:
- TNF-α stimulated proliferation in primary cell cultures (bone explants, marrow samples) in a dose-dependent manner.
- Conversely, TNF-α inhibited proliferation in established cell lines (MG-63, HCC1).
- IL-1β stimulated proliferation in most cells, except for HCC1, where potent inhibition occurred.
Conclusions:
- Pro-inflammatory cytokines are significant regulators of osteoblast-like cell proliferation.
- Cellular responses to these cytokines are cell-type specific.
- Discrepant results between primary cultures and established cell lines highlight the importance of selecting appropriate models for in vitro studies on osteopenia mechanisms in IBD.
Abstract:
Children with inflammatory bowel disease are known to be at risk of osteopenia. The cause of this osteopenia is likely to be multifactorial, but the inflammatory process with its characteristic overproduction of cytokines has been implicated. To investigate this possible contribution of the disease activity to the development of osteopenia, we performed in vitro assays of the proliferation of osteoblast-like cells of differing origins in response to the inflammatory cytokines tumor necrosis factor-alpha and IL-1/beta. Osteoblast-like cells derived from pediatric bone explants, adherent stromal cells derived from bone marrow (osteoprogenitors), MG-63 osteosarcoma cells, and SV-40 virally transformed osteoprogenitor cells (HCC1) were studied. Tumor necrosis factor-alpha stimulated the proliferation of cells in primary cultures (i.e. from explants and marrow samples) in a linear, dose-dependent manner. In contrast, inhibition of proliferation was observed with the established cell lines (MG-63 and HCC1). IL-1beta stimulated proliferation of all cells apart from the immortalized human bone marrow cell line, HCC1, in which case potent inhibition was observed. We conclude that proinflammatory cytokines are potent regulators of osteoblast-like cell proliferation, and that the responses are specific to cell type. The opposite results obtained with established cell lines compared with the primary cultures suggest that careful consideration should be given to choosing the most suitable cell line for in vitro studies relating to in vivo mechanisms predisposing to osteopenia.