scholarly journals Development of selective bispecific Wnt mimetics for bone loss and repair

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tristan W. Fowler ◽  
Troy L. Mitchell ◽  
Claudia Y. Janda ◽  
Liqin Xie ◽  
Shengjiang Tu ◽  
...  
Keyword(s):  
Bone Mass ◽  
Low Density Lipoprotein ◽  
Wnt Signaling Pathway ◽  
Density Lipoprotein ◽  
Long Bone ◽  
Mineral Density ◽  
Long Bone Fracture ◽  
Density Lipoprotein Receptor ◽  
Building Effects ◽  
Related Proteins

AbstractThe Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.

scholarly journals Common Polymorphism in theLRP5Gene May Increase the Risk of Bone Fracture and Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Guang-Yue Xu ◽  
Yong Qiu ◽  
Hai-Jun Mao
Keyword(s):  
Bone Fracture ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Bone Diseases ◽  
Case Control Studies ◽  
Mineral Density ◽  
Increased Risk ◽  
Density Lipoprotein Receptor ◽  
Independent Case

The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in bone mineral density and types of bone diseases. The present study was aimed at examining the association ofLRP5rs3736228 C>T gene with bone fracture and osteoporosis by meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association of theLRP5gene with bone fracture and osteoporosis risks. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (ORs) and their corresponding 95% confidence interval (95% CI) were calculated. An updated meta-analysis was currently performed, including seven independent case-control studies. Results identified that carriers of rs3736228 C>T variant in theLRP5gene were associated with an increased risk of developing osteoporosis and fractures under 4 genetic models but not under the dominant model (OR = 1.19, 95% CI = 0.97~1.46, andP=0.103). Ethnicity-subgroup analysis implied thatLRP5rs3736228 C>T mutation was more likely to develop osteoporosis and fractures among Asians and Caucasians in majority of subgroups. These results suggest that there is a modest effect of theLRP5rs3736228 C>T on the increased susceptibility of bone fracture and osteoporosis.

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