Alghamdi, Arwa Saeed (2025) Investigating the role of Insulin-like Growth Factor (IGF) axis in stem cell based periodontal bone regeneration in osteoporotic conditions. PhD thesis, University of Leeds.
Abstract
Osteoporosis and periodontal disease share common risk factors and are
both prevalent in the elderly population. The use of stem cells has given hope
to in various disciplines including periodontal regeneration. This project aims
to characterise periodontal ligament stem cells isolated from postmenopausal
osteoporotic patients (OP-PDLSCs) and study their osteogenic differentiation
along with exploring the potential role of Insulin-like Growth Factor (IGF) axis,
which is known to be highly linked to osteogenesis, in this process. OP-
PDLSCs (n=3) were studied in comparison to healthy PDLSCs (H-PDLSCs)
(n=4). Characterisation for clonogenicity, proliferation rate and surface marker
expression was carried out using colony forming unit-fibroblasts, population
doubling time and flow cytometry assays respectively. Osteogenic
differentiation was assessed using alkaline phosphatase (ALP), and alizarin
red (ARS) staining and mineralisation nodules quantification assay. RT-qPCR
was used to investigate the gene expression of osteogenic and bone
remodelling markers, estrogen receptors (ERs) and IGF axis. ELISA was
utilised to study the protein expression of IGF binding protein 4 (IGFBP-4) and
its protease (PAPP-A).
Compared to controls, clonogenic and proliferative capacities were lower in
the osteoporotic group. Flow cytometry indicated a similar cell surface
markers expression for all markers assessed (CD73+, CD90+, CD105+, CD14-
, CD19-, CD45-) except for CD34- and HLADR-, where the expression was
slightly higher in the osteoporotic group. ALP and ARS showed lower
osteogenic differentiation and mineralisation in OP-PDLSCs. Gene
expression showed comparable to lower relative expression levels for
RUNX2, ALPL, ColI⍺ 1, POSTN, OCN, RANKL, ERs and higher levels for
OPG in OP-PDLSCs. Gene expression showed overall lower expression in
OP-PDLSCs samples for all IGF axis members except for IGF-1
(inconsistent), IGFBP-2, IGFBP-4 and PAPP-A (higher). Protein levels for
IGFBP-4 and PAPP-A were higher in OP-PDLSCs. In conclusion, OP-
PDLSCs showed similar phenotypic characteristics to H-PDLSCs with a trend
of lower osteogenic differentiation and mineralisation capacities. Further
investigations on IGFBP-4 are needed as it could be a target to enhance
osteogenic regenerative capacity in postmenopausal OP-PDLSCs.
Metadata
| Supervisors: | El-Gendy, Reem and Meade, Josie and Jones, Elena and McKechnie, Alasdair |
|---|---|
| Keywords: | Periodontal stem cells, osteoporosis, IGF, periodontal regeneration |
| Awarding institution: | University of Leeds |
| Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) |
| Date Deposited: | 13 Jan 2026 13:57 |
| Last Modified: | 13 Jan 2026 13:57 |
| Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:37604 |
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