title: Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats.
abstract: The bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants. The inhibitors of cathepsin K (CatK) significantly affect bone turnover, bone mineral density (BMD) and bone strength in the patients with osteoporosis. Therefore, we hypothesised that the application of a CatK inhibitor (CatKI) could increase the osseointegration of endosseous implants under osteoporotic conditions. Odanacatib (ODN), a highly selective CatKI, was chosen as the experimental drug. Sixteen rats were randomised into 4 groups: sham, ovariectomy (OVX) with vehicle, OVX with low-dose ODN (5 mg/kg) and OVX with high-dose ODN (30 mg/kg). Titanium implants were placed into the distal metaphysis of bilateral femurs of each OVX rat. After 8 weeks of gavaging, CatKI treatment increased the removal torque, BMD and bone-to-implant contact (BIC). Moreover, high-dose CatKI exerted a better influence than low-dose CatKI. Furthermore, CatKI treatment not only robustly suppressed CatK gene (CTSK) expression, but also moderately reduced expression of the osteoblast-related genes Runx2, Collagen-1, BSP, Osterix, OPN, SPP1 and ALP. Thus, CatKI could affect the osteoblast-related genes, although the balance of bone turnover was achieved mainly by CatK inhibition. In conclusion, CatKI prevented bone loss and aided endosseous implantation in osteoporotic conditions.
authors.affiliation: Department of Oral Implantology, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Oral Implantology, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Ke-Yi
authors.initials: KY
authors.lastname: Hao
authors.affiliation: Department of Oral Implantology, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Oral Implantology, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Xi-Yuan
authors.initials: XY
authors.lastname: Ge
authors.affiliation: Department of Oral Implantology, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016348:Osseointegration / Q000187:drug effects; D010052:Ovariectomy; D019736:Prostheses and Implants; D011480:Protease Inhibitors / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014025:Titanium / Q000494:pharmacology*; D019415:Torque; D055114:X-Ray Microtomography
chemical_list: D011480:Protease Inhibitors; D014025:Titanium; D056657:Cathepsin K