Table I. Location, function, stimulation, regulation levels, and effected cells for the genes and proteins of interest.
| Location | Function | Stimulation | Regulation levels | Affected cell | |
|---|---|---|---|---|---|
| GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) | Most tissues and cells in the body | Break down glucose; activation and initiation of apoptosis | Used as loading control for real time polymerase chain reaction (PCR) | ||
| DMP-1 (Dentin matrix acidic phosphoprotein) | Osteocyte (surface) | Key regulator of odontoblast differentiation and also promotes mineralization of bone and dentin23 | Highly expressed during the mineralization of the bone matrix | Deficiencies include flawed dentin development, hypomineralization | Osteoclast |
| MEPE/OF 45 (Extracellular phosphoglycoprotein/Osteocyte/Osteoblast Factor-45) | Osteocyte (surface and inside) | Regulate biomineralization and mineral metabolism | Highly expressed during the mineralization of the bone matrix23 | High levels can adversely affect bone mineralization Downregulated in osteoporosis bone24 |
Osteoclast |
| SOST (Sclerostin) | Mature osteocyte (inside cell) | Controls rapid bone formation23 | Bone formation—as a negative regulator | Patients with mutations in the SOST gene can have overgrowth of the skeleton Mechanical loading may also reduce sclerostin expression25 |
Osteoblast (negative) |
| E-11 (Podoplanin) | Osteocytes (surface) | Promotes formation and elongation of osteocyte dendritic processes and is important for osteocyte cell activity | May control osteocyte morphology | Upregulated during fracture repair | Osteocyte |
| iNOS (Nitric oxide synthase inducible) | Osteocytes | Produced in response to infection or inflammatory cytokines Osteocytes respond to mechanical stimulation by expressing nitric oxide (NO)25 |
Released in response to mechanical strain or fluid-flow shear stress Increased on tension side during orthodontic tooth movement26 |
Osteoclast | |
| eNOS (Nitric oxide synthase, endothelial cells) | Osteocytes | An early mechanical response gene that promotes osteoclastogenesis, inhibits the production of prostaglandin E2, and disrupts gap junctions Osteocytes respond to mechanical stimulation by expressing NO25 |
Released in response to mechanical strain or fluid-flow shear stress Increased on tension side during orthodontic tooth movement26 |
Osteoblast | |
| OPG (Osteoprotegerin) | Both osteoblasts and osteocytes (surface) | Neutralizes RANKL and prevents the RANKL gene from binding to RANK | In competition with RANK; blocks bone resorption27 | A key regulator of osteoclastogenesis in the periodontal ligament during tooth movement28 | Osteoclast |
| RANKL (Receptor activator for nuclear factor κ B ligand) | Osteoblasts and osteocytes (surface) | Encourages bone resorption and helps osteoclast differentiation during the bone remodeling process | Produced in abundance during orthodontic tooth movement and periodontitis29 | RANKL activates RANK and the two bind together to initiate osteoclast activity; regulator of osteoclastogenesis | Apoptotic osteocytes recruit osteoclasts |
| SPP1/OPN (Secreted phosphoprotein 1/Osteopontin) | Both osteoblasts and osteocytes (surface and inside) | Mediates the osteoclast attachment to bone | Bone turnover, wound healing, and inflammatory diseases Has been shown to be elevated in a number of tumor types, and its downregulation reduces tumorigenicity |
Required for stress-induced bone remodeling because it is necessary for efficient osteoclast action15 | Osteoclast |
| PGES2 (Prostaglandin E synthase 2) | Osteocyte | Helps convert prostaglandin H2 to a more stable prostaglandin E2 (lipid) | Bone loss and during orthodontic tooth movement | Released by osteocyte in response to mechanical strain or fluid-flow shear stress | Osteoclast |