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Updated: Aug 7, 2026
Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis
Published on: January 12, 2015
Cholecystokinin-antagonist lorglumide inhibits osteogenic differentiation in human bone marrow stem cells
Catharina Marques Sacramento1, Márcio Zaffalon Casati1, Enilson Antonio Sallum1
1Departamento de Prótese e Periodontia, Divisão de Periodontia, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
Background:
The relationship between gastrointestinal hormones and bone metabolism has gained significant attention, but the specific role of cholecystokinin (CCK) in bone homeostasis remains largely unexplored. This study aimed to evaluate the role of the CCK pathway in osteogenic differentiation by blocking its mechanisms in human bone marrow stem cells (hBMSCs).
Methods:
hBMSCs were exposed to Lorglumide, a CCK signaling pathway inhibitor, under osteogenic conditions. Cell viability, osteogenic differentiation, RT-qPCR analysis of CCK, FOS, OCN, and RUNX2, IP3 receptor phosphorylation, alkaline phosphatase (ALP) activity, and calcium concentration (Ca2) were assessed to elucidate Lorglumide's effects on osteogenesis and related mechanisms.
Results:
Lorglumide reduced hBMSC viability at concentrations ≥30 μM over 14 days. Mineralization assays revealed dose-dependent inhibition, with 20 μM maintaining mineralization comparable to controls. RT-qPCR showed that Lorglumide suppressed CCK expression and altered osteogenic gene expression (FOS, RUNX2, OCN). Lorglumide decreased Ca2 concentration compared to osteogenic medium (OM) and reduced ALP activity, indicating its inhibitory effect on key osteogenic mechanisms.
Conclusion:
Lorglumide inhibits hBMSC osteoblastic differentiation, suggesting a possible role for the CCK signaling pathway in bone metabolism. These findings emphasize the involvement of gastrointestinal hormones in bone homeostasis, suggesting new therapeutic opportunities targeting hormonal regulation to promote bone health. Further studies are needed to explore the underlying mechanisms and potential clinical applications of modulating CCK pathways in bone-related disorders.
Insights
Blocking the cholecystokinin (CCK) pathway with Lorglumide inhibits human bone marrow stem cell (hBMSC) osteoblastic differentiation. This suggests CCK signaling influences bone metabolism and homeostasis.
Area of Science:
- Endocrinology
- Bone Biology
- Stem Cell Research
Background:
- Gastrointestinal hormones and bone metabolism link is gaining attention.
- The specific role of cholecystokinin (CCK) in bone homeostasis is largely unexplored.
- This study investigates CCK's role in osteogenic differentiation.
Purpose of the Study:
- To evaluate the role of the CCK pathway in osteogenic differentiation.
- To block CCK mechanisms in human bone marrow stem cells (hBMSCs).
Main Methods:
- hBMSCs were treated with Lorglumide, a CCK inhibitor, under osteogenic conditions.
- Assessed cell viability, osteogenic differentiation, gene expression (CCK, FOS, RUNX2, OCN), IP3 receptor phosphorylation, alkaline phosphatase (ALP) activity, and calcium concentration.
- Evaluated Lorglumide's effects on osteogenesis and related mechanisms.
Main Results:
- Lorglumide reduced hBMSC viability at concentrations ≥30 μM.
- Mineralization assays showed dose-dependent inhibition by Lorglumide.
- Lorglumide suppressed CCK expression, altered osteogenic gene expression, decreased calcium concentration, and reduced ALP activity.
Conclusions:
- Lorglumide inhibits hBMSC osteoblastic differentiation.
- Suggests a role for the CCK signaling pathway in bone metabolism and homeostasis.
- Highlights potential therapeutic targets for bone health through hormonal regulation.
