Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain.

Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain.
Cell Metab. 2020 Oct 03;:
Authors: Zou W, Rohatgi N, Brestoff JR, Li Y, Barve RA, Tycksen E, Kim Y, Silva MJ, Teitelbaum SL
Abstract
Adipocytes control bone mass, but the mechanism is unclear. To explore the effect of postnatal adipocyte elimination on bone cells, we mated mice expressing an inducible primate diphtheria toxin receptor (DTR) to those bearing adiponectin (ADQ)-Cre. DTR activation eliminates peripheral and marrow adipocytes in these DTRADQ mice. Within 4 days of DTR activation, the systemic bone mass of DTRADQ mice began to increase due to stimulated osteogenesis, with a 1,000% expansion by 10-14 days post-DTR treatment. This adipocyte ablation-mediated enhancement of skeletal mass reflected bone morphogenetic protein (BMP) receptor activation following the elimination of its inhibitors, associated with simultaneous epidermal growth factor (EGF) receptor signaling. DTRADQ-induced osteosclerosis is not due to ablation of peripheral adipocytes but likely reflects the elimination of marrow ADQ-expressing cells. Thus, anabolic drugs targeting BMP receptor inhibitors with short-term EGF receptor activation may be a means of profoundly increasing skeletal mass to prevent or reverse pathological bone loss.
PMID: 33027637 [PubMed - as supplied by publisher]

Source: Cell Metabolism - October 3, 2020 Category: Cytology Authors: Zou W, Rohatgi N, Brestoff JR, Li Y, Barve RA, Tycksen E, Kim Y, Silva MJ, Teitelbaum SL Tags: Cell Metab Source Type: research