Castanon, Mariah

Hum, Julia M., Ph.D

Marshall, Vince, OMS-3

Wacker, Bryan, OMS-3

English

Marian University Indianapolis

MUShare 
MU-COM Research Day College of Osteopathic Medicine 
2020 
Notum: A Novel Regulator of Bone and Its Implications in 
Osteoporosis 
Mariah Castanon 
Marian University - Indianapolis 
Vince Marshall OMS-3 
Marian University - Indianapolis 
Bryan Wacker OMS-3 
Marian University - Indianapolis 
Julia M. Hum Ph.D 
Marian University - Indianapolis 
Follow this and additional works at: https://mushare.marian.edu/mucom_rd 
 Part of the Medicine and Health Sciences Commons 
Recommended Citation 
Castanon, Mariah; Marshall, Vince OMS-3; Wacker, Bryan OMS-3; and Hum, Julia M. Ph.D, "Notum: A Novel 
Regulator of Bone and Its Implications in Osteoporosis" (2020). MU-COM Research Day. 173. 
https://mushare.marian.edu/mucom_rd/173 
This Poster is brought to you for free and open access by the College of Osteopathic Medicine at MUShare. It has 
been accepted for inclusion in MU-COM Research Day by an authorized administrator of MUShare. For more 
information, please contact emandity@marian.edu. 
• Osteoporosis is a silent, dangerous pathology 
frequently undiagnosed until patients experience a 
major fracture. 
• About 1 in 2 women and 1 in 4 men ages 50 and 
above will experience bone fractures due to 
osteoporosis. 
• Fractures from osteoporosis may lead to a 20% 
increase in mortality. 
• Notum is a lipase, primarily expressed in the liver, that 
inhibits the Wnt signaling pathway. The Wnt pathway 
is involved in growth, development, and healing. 
• Recently, inhibition or absence of Notum led to 
increased endocortical bone formation and thickness 
via osteoblast activity in a mouse model. 
• Potentially, modifying factors that affect Notum 
expression could promote anabolic bone growth. 
Notum expression is affected by 
mechanical loading and aging.
HYPOTHESIS
Notum: A Novel Regulator of Bone 
and Its Implications in Osteoporosis
Mariah Castanon, Vince Marshall, Bryan Wacker, & 
Julia M. Hum
Division of Biomedical Sciences
Marian University College of Osteopathic Medicine
#HumLab
@DrJuliaHum
Notum expression increases in aged bone
Embryonic
Young 
Old
Notum
B-actin
Figure 3. A) Whole bone samples were taken from different aged mice, protein
extracted and evaluated by Western blot. “Embryo.” (embryonic) sample age:
embryonic week 12. “Young” samples: 1 week, 4 weeks, 8 weeks. “Old” samples: 15
weeks, 35 weeks, 55 weeks. B) The software program ImageJ was used to quantify
Notum and B-actin levels (*p<0.05).
RESULTS
A)
B)
Figure 1. A) Cells from an osteocyte cell line, MLOY4, were cultured,
harvested and subjected to mechanical loading mimicked via orbital shear
stress for 15 minutes or 2 hours. Protein was then isolated and evaluated by
Western blot. B) The software program ImageJ was used to quantify Notum
and B-actin levels.
Mechanical loading decreases Notum 
expression
*
• Mechanical loading decreases Notum protein 
expression in an osteocyte cell line, MLOY4. 
• Mechanical loading has no affect on Notum 
expression in an osteoblast cell line, MC3T3-E1. 
• Aging increases the expression of the Notum gene in 
a mouse model.
The Role of Notum in Bone’s 
Response to Mechanical 
Loading and Aging
SUMMARY
0
0.5
1
1.5
2
Embryonic Young Old
D
en
si
tr
om
et
ry
U
ni
ts
Notum
B-actin
A)
B)
NOTUM
Static
15 min 
2 hour
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
static 15 min 2 hour
D
en
si
tr
om
et
y 
U
ni
ts
FUTURE DIRECTIONS
• Continue trials on assessing mechanical loading affect 
on Notum expression in osteoblast cell line,  MC3T3-
E1.
• Future studies in inhibiting Notum expression in bone 
via a small molecule inhibitor and an siRNA will be 
conducted to investigate a potential novel approach to 
promoting anabolic bone growth.
Mechanical loading has no effect on 
Notum expression 
Figure 2. A) Cells from an osteoblast cell line, MC3T3-E1, were cultured, harvested
and subjected to mechanical loading mimicked via orbital shear stress for 15 minutes,
30 minutes, 1 hour, and 2 hours. Protein was then isolated and evaluated via Western
blot. B) The software program ImageJ was used to quantify Notum and B-actin levels.
RESULTS
Static
B-actin
1 hour
2 hours 


Notum: A Novel Regulator of Bone and Its Implications in Osteoporosis

https://mushare.marian.edu/cgi/viewcontent.cgi?article=1172&context=mucom_rd

Notum: A Novel Regulator of Bone and Its Implications in Osteoporosis

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