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Therefore, the PRKO bone phenotype may be due to a lack of nPR signaling rather than the changes in systemic sex hormone levels [30], [31], [32], [43], [44].
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The independent manifestation of the cartilage and bone phenotypes may be due to the fact that osteoclasts are not affected in Mmp13−/− mice.
These results suggest that bone phenotypes may be important yet tractable features of RTT and should be considered in future studies aimed at developing pharmacological and generic interventions for the disorder.
Therefore, both bone mass phenotypes may be considered risk factors for OA initiation.
Previous reports that male TH mice experience increases in blood glucose levels with age and develop hyperglycemia, hyperleptinemia, and hyperinsulemia [31], [32] are consistent with our results and suggest that diabetic phenotypes may be associated with bone loss in male TH mice.
However, it is also possible that significant amelioration of bone phenotypes may also be achieved using pharmacological strategies.
These additional phenotypes may be subclinical requiring additional clinical evaluation to detect (e.g. temporal bone abnormalities detected by CT in a hearing impaired patient with an uncertain variant in SLC26A4, the gene associated with Pendred syndrome).
Using both computer- and human-extracted imaging phenotypes may be clinically valuable.
Phenotypes may be quantitative or qualitative.
Milder phenotypes may be clinically overlooked [ 147].
Our data suggest that this is also present in MGUS patients, and that dysregulated bone marrow redox may be a unifying phenotype that drives the development of paraproteinaemia.
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