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Gremlin1 is required for skeletal development and postnatal skeletal homeostasis
Ernesto Canalis1, Kristen Parker, Stefano Zanotti
1Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA. ecanalis@stfranciscare.org
Inactivating gremlin 1 (Grem1) causes skeletal abnormalities and osteopenia in mice. Bone loss is partially reversed in older females, but persists in males, indicating Grem1
Area of Science:
- Skeletal Biology
- Developmental Biology
- Bone Physiology
Background:
- Gremlin 1 (Grem1) antagonizes bone morphogenetic proteins (BMPs), inhibiting osteoblastogenesis and leading to osteopenia.
- While Grem1 inactivation causes developmental defects, its postnatal skeletal effects remain unclear.
Purpose of the Study:
- To investigate the role of Grem1 in postnatal skeletal homeostasis.
- To determine the consequences of global Grem1 inactivation on the adult skeleton.
Main Methods:
- Homologous recombination was used to inactivate the Grem1 gene in mice.
- Skeletal abnormalities were assessed, including limb and bone formation.
- Bone histomorphometry and microarchitecture analyses were performed on femurs and vertebrae.
Main Results:
- Grem1 null mice displayed skeletal abnormalities, reduced body weight, and shortened femurs.
- Early-stage Grem1 null mice showed decreased bone volume and increased bone formation.
- Bone volume recovery was observed in older Grem1 null females but not males, with persistent vertebral osteopenia in males.
Conclusions:
- Grem1 is crucial for both skeletal development and postnatal skeletal homeostasis.
- Grem1 inactivation induces osteopenia with a partial, sex-dependent reversal linked to increased bone formation.
- These findings highlight Grem1's complex role in maintaining bone health throughout life.
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