title: Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects.
abstract: Osteoporosis is a prominent disorder affecting over 200 million people worldwide. Recently, semaphorins have been implicated in the cell-cell communication between osteoclasts and osteoblasts and have been associated with the progression of osteoporosis. Previously, we demonstrated that knockdown of semaphorin4d (Sema4d) using siRNA delivered with a bone-targeting system prevented bone loss in an osteoporotic animal model. Here, we used this bone-specific technology containing siRNA-Sema4d and fabricated a PLLA scaffold capable of enhancing bone repair following fracture. We investigated the ability of the implant to release siRNA-Sema4d into the surrounding tissues over time and to influence new bone formation in a 3 mm femur osteoporotic defect model in ovariectomized rats. Delivery of the bone-targeting system released from PLLA scaffolds began 2 hours post-implantation, peaked at 1 day, and was sustained over a 21 day period. μCT analysis demonstrated a significantly higher bone volume/total volume bone mineral density and number of osteoblasts in the rats that were transplanted with scaffolds loaded with siRNA-Sema4d. These results confirm the specific role of Sema4d in bone remodeling and demonstrate that significant increases in the speed and quality of new bone formation occur when siRNA-Sema4d is delivered via a PLLA scaffold.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People's Republic of China.|Department of Dental Implantology, School and Hospital of Stomatology, Wuhan University, People's Republic of China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People's Republic of China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Wei
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People's Republic of China.|Department of Restorative, Preventive and Pediatric Dentistry, University of Bern, Switzerland.|Department of Periodontology, Nova Southeastern University, Fort Lauderdale, Florida, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miron
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People's Republic of China.|Department of Dental Implantology, School and Hospital of Stomatology, Wuhan University, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People's Republic of China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D018786:Bone Substitutes; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D010010:Osteoclasts / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D017208:Rats, Wistar; D039961:Semaphorins / Q000235:genetics* / Q000378:metabolism; D054457:Tissue Scaffolds
chemical_list: D015703:Antigens, CD; D018786:Bone Substitutes; C093224:CD100 antigen; D034741:RNA, Small Interfering; D039961:Semaphorins