Table 4.
Role of Estrogens on Connective Tissue Derived Stem Cell Stemness
| Cell type | PDLSCs |
|||||
|---|---|---|---|---|---|---|
| Sex | Animal model, age | In vitro, in vivo | Hormone treatment | Response | Study | |
| Rat cells | ||||||
| PDLSCs | F | Sprague-Dawley rats, 3-month old | In vitro | 10−7 M E2 | E2 treatment: increased osteogenic potential through both ERα and ERβ. | Zhang et al.77 |
| PDLSCs | F | Sprague-Dawley rats, 3-month old | In vitro | 10−7 M E2; ovx | Cells from ovx rats: higher proliferation rates and lower osteogenic potential than cells from sham or ovx cells treated with E2; cells from all groups grew well on nHAC/PLA scaffold, although cells from ovx rats had lower osteogenic potential. | Ling-Ling et al.52 |
| Human cells | ||||||
| PDLSCs | F | Human, 18, 19, and 22-year old | In vitro | 10−7, 10−8, 10−9 M E2 | E2 treatment: increased osteogenic potential in a dose-dependent manner; both ERα and ERβ were important for osteogenic differentiation. | Pan et al.79 |
| PDLSCs | F and M | Human, 18–20-year old | In vitro | 10−6, 10−7, 10−8 M E2 | Treatment with 10−7 M E2: increased proliferation rates, proportion of cells in G2/M+S phase of the cell cycle, and expression of stemness-related genes; the PI3K/AKT pathway was involved E2 treatment in general: improved the proliferation, stemness, and differentiation potential of cells in long-term culture. |
Ou et al.78 |
| PDLSCs | N/A | Human, 12–16-year old | In vitro | 10−7 M E2 | E2 treatment: increased osteogenesis through activation of the Wnt/β-catenin pathway | Jiang et al.80 |
| Rats | ||||||
| PDLSCs | F | Sprague-Dawley rats, 3-month old | In vivo | ovx | ovx animals: contain more PDLSCs; proliferate faster but decrease sooner | Zhang et al.77 |
| PDLSCs | F | Sprague-Dawley rats, 3-month old | In vivo | 10−7 M E2; ovx | In seeded nHAC/PLA scaffolds implanted into SCID mice, all cell types led to new bone growth, with cells from ovx rats generating the least | Ling-Ling et al.52 |
| TDSCs | ||||||
| TDSCs | M | C57BL/6J mice, 6-month old | In vivo | None, but ERβ−/− mice compared to WT | Achilles tendon injury model: WT: more ERβ+ cells found in injured than noninjured animals ERβ−/−: lower cell density and higher adipocyte and blood vessel accumulation in scar site than WT |
Bian et al.81 |
| TDSCs | M | Sprague-Dawley rats, 6-week old | In vitro | 10−5, 10−7, 10−9 M LY3201 (ERβ agonist) | Treatment with 10−7 M LY3201: promoted cell proliferation; inhibited adipogenesis; other concentrations had no effect. | Bian et al.81 |
| CPCs | ||||||
| CPCs | F and M | Human, with OA | In vitro | 0.02 or 0.15 ng/mL E2 | F: greater percentage of cells expressed ERz and ERβ E2 treatment: F and M: increased ERα and decreased ERβ expression F: increased chondrogenesis |
Koelling and Miosge82 |
| FCSC | ||||||
| FCSCs | M | New Zealand White rabbits, 12-week old | In vivo | 0.1 mL of 100 ng/mL Sost once weekly for 7 weeks | Sclerostin (Wnt pathway inhibitor) treatment after post-traumatic OA induction: increased FCSC number in TMJ superficial zone; decreased joint damage; reduced joint swelling | Embree et al.83 |
| FCSCs | F | C57BL/6 mice, 3- or 13-week old | In vivo | 0.01 mg/60 days E2 pellet; ovx | E2 treatment in: Young mice: promoted chondrogenesis through ERα through upregulation of Sost Mature mice: promoted chondrogenesis and anabolic gene expression through ERα |
Robinson et al.84 |
CPC, chondrogenic progenitor cell; FCSC, fibrocartilage stem cell; nHAC/PLA, nano-hydroxyapatite/collagen/poly(L-lactide); OA, osteoarthritis; PDLSCs, periodontal ligament stem cells; SCID, severe combined immunodeficient; Sost, sclerostin; TDSC, tendon-derived stem cell; TMJ, temporomandibular joint.