Ostecocyte Intergrity and Bone Remodeling
Description: PUBLIC HEALTH RELEVANCE: Osteoporosis results from the accelerated birth of new remodeling sites and/or to alterations to the activities of the cells, osteoclasts or osteoblasts, within those remodeling sites, leading to excessive resorption, too little formation or both. Understanding of the critical Activation step or the "On-Switch" to start bone remodeling is very limited. Our studies have revealed that osteocyte apoptosis, i.e., regulated death of osteocytes, controls activation of bone remodeling in response to skeletal unloading, fatigue (wear & tear) bone microdamage and estrogen loss. In the case of fatigue microdamage in bone, the controlled death of groups of osteocytes triggers their viable neighbor osteocytes to produce RANKL biochemical signals to recruit osteoclasts that resorb bone at the start of remodeling. In the current studies we will test whether this osteocyte apoptosis triggering of signaling from non-dying neighbor cells is actually a universal mechanism for a range of challenges that turn on bone remodeling and can lead to bone loss. In a related series of studies, we will examine how dying osteocytes signal their surviving neighbors to "call for help." We will explore parallels wit the cell death and the "help" signaling responses evoked from surviving cells in stroke and heart attack, with particular focus on the role of gap junctions channels and pannexin channels. Understanding these biological mechanisms may open a new window for novel therapeutic targets that to modulate bone remodeling and prevent osteoporosis and bone fragility.
Funding type: research
Funder scheme: R01
Start date: 1992-09-15
End date: 2021-02-28
Investigator: MITCHELL B SCHAFFLER
Institution: CITY COLLEGE OF NEW YORK
Funded outputs count: 105
Funder award ID: R01AR041210
OpenAlex ID: G2639953458