Title: MSC regulator accordion

PPARg

Peroxisome proliferator-activated receptor gamma

- Transcription factor
- Inhibits increase in bone mass
- Down regulates osteoblast differentiation
- Up regulates adipocyte differentiation

C/EBP

CCAAT-enhancer-binding proteins

- Transcrption factorts (6 in total)
- Interact with CCAAT box in promotor
- Regulates PPARg

Osterix and Runx2

- Transcrption factors
- Enhance bone formation
- Up regulate osteoblast (and osteocyte) and chondrocyte differentiation

HTRA1

High-temperature requirement serine protease A1

- Positively regulates osteogenesis
- Repression of HTRA1 gene expression alters lineage commitment of differentiating human bone marrow-derived MSCs, specifically reducing osteogensis and increasing adipogenesis [4]

Other Factors

Diabetes

- Type I and type II associated with increased risk of osteoporosis
- BMSCs are dysfunctional under hyperglycemic conditions
- Increased apoptosis senescence and loss of osteogenic capacity
- Increased adipogenic potential

Estrogen

- Estrogen stimulates BMSCs osteogenesis via estrogen receptors
- BMSCs osteogenesis/adipogenesis defective in postmenopausal women
- Estrogen loss results in bone loss

Bisphosphonates

- A synthetic compound containing two PO3 groups
- High affinity for hydroxyapatite, becomes imbedded in bone
- As osteoclasts resorb bone, bisphosphonates are engulfed and causes osteoclasts to inactivate, detach from bone, and stop bone resorption
- Used to treat osteoporosis and other bone loss diseases