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The Effects of Indian Hedgehog Deletion on Mesenchyme Cells: Inducing Intermediate Cartilage Scaffold Ossification to Cause Growth Plate and Phalange Joint Absence, Short Limb, and Dwarfish Phenotypes
- Source :
- Stem Cells and Development. 27:1412-1425
- Publication Year :
- 2018
- Publisher :
- Mary Ann Liebert Inc, 2018.
-
Abstract
- The endochondral ossification plays a critical role in vertebrate limb development and skeletal homeostasis, where limb mesenchyme cells form an intermediate cartilage scaffold that develops into growth plates and then replaced by bone. Although Indian hedgehog (Ihh) is known to control the hypertrophic differentiation process of chondrocytes, its role from the mesenchyme cells to the early stages of chondrogenesis is unclear. To define the function of Ihh in the mesenchymal cell's early stages of chondrogenesis, we specifically delete Ihh in Prx1-expressed mesenchyme cells at E9.5 using Prx1-Cre;Ihh(fl/fl);Rosa26(-ZsGreen1) mice. We found that deleting Ihh in the mesenchyme cells results in an early and quick ossification of the intermediate cartilage scaffold, causing the growth plate and phalange joint absence, short limbs, and dwarfishness. The green fluorescent protein (GFP)-positive cells derived from deleted Ihh mesenchyme cells overlap with von Kossa- and osteocalcin-positive staining area. These deleted Ihh/GFP-positive cells isolated from Prx1-Cre;Ihh(fl/fl);Rosa26(-ZsGreen1) newborn mice had osteogenic differentiation by showing a positive Alizarin red and von Kossa staining, as well as an enhanced Col1a1, osteocalcin, and Runx2 expression. Our findings demonstrate that deleting Ihh in mesenchyme cells during early limb development promotes intermediate cartilage scaffold ossification, which prevents growth plate formation that causes phalange joint absence, short limb, and dwarfish phenotype.
- Subjects :
- 0301 basic medicine
Indian hedgehog
Mesenchyme
Dwarfism
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Original Research Reports
Osteogenesis
medicine
Animals
Humans
Limb development
Hedgehog Proteins
Growth Plate
Phalangeridae
Endochondral ossification
Homeodomain Proteins
Bone Development
Ossification
Cartilage
Gene Expression Regulation, Developmental
Extremities
Mesenchymal Stem Cells
Cell Biology
Hematology
biology.organism_classification
Chondrogenesis
Cell biology
body regions
RUNX2
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Vertebrates
medicine.symptom
Developmental Biology
Subjects
Details
- ISSN :
- 15578534 and 15473287
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Stem Cells and Development
- Accession number :
- edsair.doi.dedup.....934892a2c8edd27bee45830fc713bcdb