Poster CC19 - Anti-fragility effects on bone in Casp2 overexpressing mice

Friday, October 25, 2024

3:30 PM - 4:30 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Sai Vijay Trilochan Tadi

Graduate Researcher
University of Texas at San Antonio
San Antonio, Texas, United States

Co-Author(s)

Benjamin G. Johnson, MD (he/him/his)

Pediatrics Resident
Emory University Pediatrics Residency program
Atlanta, Georgia, United States
Alisa Isaac, PhD (she/her/hers)

SABER IRACDA Post-Doctoral Scholar
The University of Texas Health Science Center
San Antonio, Texas, United States
Ramaswamy Sharma, MS, PhD

Professor
University of the Incarnate Word School of Osteopathic Medicine, United States

Primary Investigator(s)

TG

Teja Guda, PhD

Jacobson Distinguished Professor of Innovation and Entrepreneurship
The University of Texas at San Antonio, United States

Introduction: Age-related osteoporosis results in millions of fractures annually, causing significant morbidity. The underlying molecular and macrostructural causes of bone loss remain poorly understood. Caspase-2 (Casp2), a cysteine aspartate protease, is involved in apoptosis and cellular stress responses. This study aims to elucidate the role of Casp2 in bone homeostasis by analyzing osteoclast activity in transgenic low-expressor (TgL), high-expressor (TgH), and wild-type (WT) mice. Key parameters measured include osteoclast surface area (Oc.S), osteoclast surface per bone surface (Oc.S/BS), number of osteoclasts (N.Oc), and number of osteoclasts per bone surface (N.Oc/BS). These parameters are critical indicators of osteoclast function and bone resorption activity.

Materials and

Methods: Osteoclast data were collected using BioQuant Osteo 2022 image analysis software in conjunction with Motic microscope software. Bone tissue samples were imaged at 40x magnification, and saved as BIF (Big Image Format) files. After imaging, the BIF files were processed using BioQuant Osteo software to extract bone-referent data and osteogenic metrics. Using the osteoclast arrays available in BioQuant, the L2 software module was utilized to identify and select osteoclasts within the region of interest in the bone samples. This process involved locating and identifying osteoclasts to gather quantitative data, focusing on Oc.S, Oc.S/BS, N.Oc, and N.Oc/BS, which provided detailed insights into osteoclast activity and density across different groups.

Results, Conclusions, and Discussions: Quantitative analysis revealed significant variations in osteoclast activity over time in transgenic low-expressor (TgL) mice, comparing both genders. The data showed changes in osteoclast surface area (Oc.S) and osteoclast density metrics over different time points. For male TgL mice, the osteoclast surface area (Oc.S) increased from 1.25 mm² at 3 months to 3.17 mm² at 24 months, while females showed an increase from 1.05 mm² to 2.30 mm². The osteoclast surface area per bone surface (Oc.S/BS) for males rose from 0.034 mm²/mm² to 0.115 mm²/mm², and for females from 0.021 mm²/mm² to 0.161 mm²/mm². The number of osteoclasts per bone surface (N.Oc/BS) for males increased from 0.321 cells/mm² at 3 months to 0.466 cells/mm² at 24 months, while females rose from 0.192 cells/mm² to 0.278 cells/mm². The total number of osteoclasts (No.C) in males increased from 12.73 to 18.45, and in females from 7 to 12.

These results indicate that osteoclast activity and bone resorption in TgL mice increase over time, with noticeable differences between males and females. The increase in osteoclast metrics such as Oc.S, Oc.S/BS, and N.Oc/BS suggests that Caspase-2 (Casp2) expression plays a pivotal role in regulating osteoclast function. The observed gender differences could be attributed to hormonal influences on bone metabolism, as males showed higher values in most osteoclast metrics compared to females. These findings align with existing research on Casp2’s impact on osteoclast differentiation and activity, highlighting its potential as a therapeutic target for managing osteoporosis. Future studies should focus on elucidating the molecular mechanisms by which Casp2 influences osteoclast function and interacts with bone homeostasis pathways. Understanding these pathways could lead to novel treatments for osteoporosis that effectively maintain bone density and strength by regulating osteoclast activity

Acknowledgements (Optional):