Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.
By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.|Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Li
L
Li
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.
Xiaozhong
X
Peng
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.
Yongbao
Y
Qin
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.
Renchong
R
Wang
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.
Jingli
J
Tang
Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Xu
X
Cui
Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Ting
T
Wang
Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Wenlong
W
Liu
Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Haobo
H
Pan
Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.
Bing
B
Li
D000818:Animals; D001843:Bone Cements / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001861:Bone Regeneration; D002460:Cell Line; D065546:Drug Liberation; D017886:Durapatite / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D018021:Lithium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D058866:Osteoporotic Fractures / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway
D001843:Bone Cements; D017886:Durapatite; D018021:Lithium Chloride