Hox genes maintain critical roles in the adult skeleton.

Autor:	Song JY; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109., Pineault KM; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705., Dones JM; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139., Raines RT; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139., Wellik DM; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705; wellik@wisc.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Mar 31; Vol. 117 (13), pp. 7296-7304. Date of Electronic Publication: 2020 Mar 13.
DOI:	10.1073/pnas.1920860117
Abstrakt:	Hox genes are indispensable for the proper patterning of the skeletal morphology of the axial and appendicular skeleton during embryonic development. Recently, it has been demonstrated that Hox expression continues from embryonic stages through postnatal and adult stages exclusively in a skeletal stem cell population. However, whether Hox genes continue to function after development has not been rigorously investigated. We generated a Hoxd11 conditional allele and induced genetic deletion at adult stages to show that Hox11 genes play critical roles in skeletal homeostasis of the forelimb zeugopod (radius and ulna). Conditional loss of Hox11 function at adult stages leads to replacement of normal lamellar bone with an abnormal woven bone-like matrix of highly disorganized collagen fibers. Examining the lineage from the Hox- expressing mutant cells demonstrates no loss of stem cell population. Differentiation in the osteoblast lineage initiates with Runx2 expression, which is observed similarly in mutants and controls. With loss of Hox11 function, however, osteoblasts fail to mature, with no progression to osteopontin or osteocalcin expression. Osteocyte-like cells become embedded within the abnormal bony matrix, but they completely lack dendrites, as well as the characteristic lacuno-canalicular network, and do not express SOST. Together, our studies show that Hox11 genes continuously function in the adult skeleton in a region-specific manner by regulating differentiation of Hox -expressing skeletal stem cells into the osteolineage. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu