We have located links that may give you full text access.
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
mTOR Inhibition Subdues Milk Disorder Caused by Maternal VLDLR Loss.
Cell Reports 2017 June 7
It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. In contrast, VLDLR deletion in the mother alters milk metabolism, which inhibits osteoclast differentiation and causes osteopetrosis in the offspring. The maternal effects are dominant. VLDLR-null lactating mammary gland exhibits higher mTORC1 signaling and cholesterol biosynthesis. Pharmacological probing reveals that rapamycin, but not statin, treatment of the VLDLR-null mother can prevent both the low bone resorption and our previously described inflammatory fur loss in their offspring. Genetic rescue reveals that maternal mTORC1 attenuation in adipocytes, but not in myeloid cells, prevents offspring osteopetrosis and fur loss. Our studies uncover functions of VLDLR and mTORC1 in lactation and osteoclastogenesis, illuminating key mechanisms and therapeutic insights for bone and metabolic diseases.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app