Document text
Principal Investigator: Pranav Soman
Organization: SYRACUSE UNIVERSITY
Fiscal Year: 2024
Award: $322,408
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Summary
Osteocytes are the most numerous cell in bone tissue, which act as mechanosensors and coordinate adaptive
bone remodeling. Current model systems have been unable to unify the mechanisms by which osteocytes to
sense mechanical stimuli, transmit signals across an extensive 3D network, and how these transient signals
drive adaptive bone remodeling by osteoblasts and osteoclasts. In this work, we will use a new bone multicellular
unit (BMU) chip that enables longitudinal visualization of mechanosensitive calcium signaling across 3D
osteocyte networks, enabling and characterization of the role of this signaling mechanism on the
mechanoadaptive response of osteoblasts and osteoclasts in normal and injured states. Using BMU-chip, this
work will test the hypothesis, ‘Discontinuity in 3D osteocyte networks alters mechanically-evoked calcium signal
propagation which in turn modulates the spatiotemporal remodeling of effector cells’ using three specific aims.
Aim 1 will define how Pulsed Unidirectional Fluid Flow Stimuli (PUFFS) modulates dynamic changes in calcium
signaling across 3D network of osteocytes. Aim 2 will determine how 3D osteocyte networks subjected to PUFFS
modulate direct and indirect signaling and osteoblastic bone formation and osteoclastic resorption activities. Aim
3 will identify how targeted disruption of 3D osteocyte networks influence calcium signaling and long-term
functional outcomes. Completion of the proposed aims will provide a comprehensive understanding of how
mechanically evoked calcium signaling across osteocyte networks modulates functional outcomes within the
BMU in normal and injured conditions. Our team, with complementary expertise in biomedical engineering, bone
cell biology, orthopedic surgery and statistical analysis is well suited to execute this project. In the future, BMU-
chips could be utilized to probe other mechanotransduction pathways, and accelerate the development and
evaluation of drugs to treat bone disease.
Terms: <3-D><3-Dimensional><3D><Ablation><Acceleration><Behavior><Biologic Models><Biological Models><Biomedical Engineering><Bone Diseases><Bone Formation><Bone Resorption><Bone Tissue><Bone remodeling><Calcium Ion Signaling><Calcium Signaling><Cell Body><Cell Communication and Signaling><Cell Function><Cell Physiology><Cell Process><Cell Signaling><Cells><Cellular Function><Cellular Mechanotransduction><Cellular Physiology><Cellular Process><Cellular biology><Co-culture><Cocultivation><Coculture><Coculture Techniques><Coin><Collagen><Cyclicity><Degenerative Arthritis><Degenerative polyarthritis><Development><Devices><Drug Evaluation><Drug Evaluation Studies><Effector Cell><Frequencies><Future><Gene Expression><Goals><Hour><In Vitro><Individual><Intracellular Communication and Signaling><Laser Electromagnetic><Laser Radiation><Lasers><Link><Liquid substance><Mechanical Signal Transduction><Mechanics><Mechanosensory Transduction><Methods><Microfluidic Device><Microfluidic Lab-On-A-Chip><Microfluidic Microchips><Model System><Modeling><Morphology><Orthopedic Surgery><Osteoarthritis><Osteoarthrosis><Osteoblasts><Osteoclastic Bone Loss><Osteoclasts><Osteocytes><Osteogenesis><Osteoporosis><Outcome><Paracrine Communication><Paracrine Signaling><Pathway interactions><Periodicity><Physiologic pulse><Production><Property><Protocol><Protocols documentation><Publishing><Pulse><Recovery><Reproducibility><Research><Rhythmicity><Role><Signal Transduction><Signal Transduction Systems><Signaling><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Stimulus><Subcellular Process><Testing><Time><Translating><Transmission><Visualization><Work><bio-engineered><bio-engineers><bioengineering><biological engineering><biological signal transduction><bone><bone cell><bone disorder><bone remodelling><bone tissue formation><cell biology><cell type><cost><cytokine><degenerative joint disease><developmental><empowerment><experiment><experimental research><experimental study><experiments><fluid><fluid flow><functional outcomes><hypertrophic arthritis><in vitro Model><in vivo Model><injured><irradiation><liquid><mechanic><mechanical><mechanical stimulus><mechanosensing><mechanotransduction><microfluidic chip><novel><osteoarthritic><pathway><response><self assembly><skeletal><skeletal disease><skeletal disorder><social role><spatiotemporal><statistical analysis><three dimensional><transmission process>