Inhibitory effect of adenovirus-mediated siRNA-targeting BMPR-IB on UHMWPE-induced bone destruction in the murine air pouch model.
Connect Tissue Res
; 53(6): 528-34, 2012.
Article
in En
| MEDLINE
| ID: mdl-22827452
ABSTRACT
OBJECTIVE:
Adenovirus expressing small interfering RNA (siRNA)-targeting BMPR-IB was locally administered into the air pouch of mice to improve bone resorption induced by ultra-high molecular weight polyethylene (UHMWPE) particles.METHOD:
Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor. The bone-implanted pouches were stimulated with the UHMWPE suspension. UHMWPE-containing mice were divided into three study groups to receive injections of adenovirus expressing BMPR-IB siRNA (BMPR-IB group), adenovirus expressing missense siRNA, and virus-free culture medium (control group) into the pouches, respectively. The tissues were harvested at 14 days after the treatment for molecular and histological analyses.RESULTS:
Adenovirus-mediated BMPR-IB siRNA treatment significantly improved UHMWPE particle-induced bone resorption, reduced TRAP and RANK gene and protein expression levels, and diminished the number of TRAP-positive cells. Furthermore, the BMPR-IB siRNA inhibited osteoclast differentiation by targeting osteoblast for the induction of osteoprotegerin formation and downregulation of receptor for activation of nuclear factor-κB ligand production.CONCLUSIONS:
This study suggested that loss of bone morphogenetic protein signaling by BMPR-IB siRNA directs osteoblasts to decrease bone destruction in part by downregulating osteoclastogenesis through the receptor for activation of nuclear factor-κB ligand-osteoprotegerin pathway. Local administration of adenovirus expressing siRNA-targeting BMPR-IB may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Resorption
/
Adenoviridae
/
Polyethylene
/
RNA, Small Interfering
/
Bone Morphogenetic Protein Receptors, Type I
/
Genetic Vectors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Connect Tissue Res
Year:
2012
Type:
Article
Affiliation country:
China