Phenotype Image Detail

Image

Caption

Characterization of the osteoblast and chondrocyte phenotype in Sostdc1^tm1Snd/Sostdc1^tm1Snd (Wise^-/-) mutants. (A) Chondrocyte proliferation as detected using BrdU. P4 Wise-/- mutants display a significant (asterisk) 63% decrease in proliferation of the round proliferative chondrocytes (rpCh), whereas no significant change in the flat proliferative (fpCh), prehypertrophic (phCh), and hypertrophic chondrocytes (hCh). Black bars depict wild-type, white bars depict Wise-/-. Insert shows the location of the different chondrocyte types within the long bone femur of a mouse. pCh; proliferating chondrocytes. (N = 4 per group). (B) Active osteoblast cell proliferation as detected using BrdU in a 1.5 month mouse. Wise-/- mutants display a significant (asterisk) 2.9 fold increase in active osteoblast proliferation of long bones at 1.5 months. (N = 4 per group). (C) Active osteoblast/osteoclast numbers counted from Toluidine Blue or Trap stained sections (Toluidine blue/Trap stained panel adjacent to chart) are quantified in Chart. A 2 fold significant increase (asterisk) in active osteoblasts is seen in 1.5 month old Wise-/- mutant long bones (arrow, blue columnar cells adjacent to trabeculae in adjacent Toluidine Blue panel). This increase in active osteoblast numbers is dependent on the presence of Lrp5 as shown by the Chart hatched bar at 1.5 month (Wise-/-;Lrp5-/-). Osteoclast numbers (adjacent Trap stained panel (red), arrow) counted from TRAP stained sections reveal a significant 58% decrease in numbers at 2.5 months of age in a Wise-/- mutant. (wild-type/mutant: osteoblasts N= 6/6 1.5 m, N= 5/3 2.5 m; osteoclasts N = 6/6 1.5 m, N= 5/3 2.5 m). (D) Bone formation rate as assayed from calcein double labeling. A significant (asterisk) 1.3 fold increase in bone formation rate is evident in Wise-/- mutant mice at 2.5 months of age. (N = 3 per group). (E) Summary of Wise Function. Wise functions as both a stimulator and an inhibitor of Wnt signaling during skeletal development. In the chondrocytes, Wise acts as a positive stimulator of Wnt signaling, whereas in the osteoblast, Wise functions as a Wnt antagonist. A loss of Wise function leads to an increase in bone mass at 1.5 to 2.5 months of age. The increase in bone mass at 1.5 months of age is attributed to an increase in osteoblast Wnt signaling and hence osteoblast proliferation, resulting increase in bone volume. Whereas, the increase in bone mass seen at 2.5 months is due to a decrease in osteoclast number possibly from increased osteoblast Wnt signaling that results in an increase in OPG levels, and resulting decrease in resorption. This potential decrease in resorption could result in the increased bone mass at 2.5 months. However at 2.5 months the bone formation rate is also increased and this would lead to the increased bone mass and increased trabecular bone volume.

This image is from Ellies DL, PLoS One 2014;9(5):e96257, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:216098

Associated
Alleles

Symbol	Name
Sostdc1^tm1Snd	sclerostin domain containing 1; targeted mutation 1, Scott Saunders

Associated
Genotypes

Allelic Composition	Genetic Background
Sostdc1^tm1Snd/Sostdc1^tm1Snd	involves: C57BL/6

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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