C - Michigan Technological University

have evolved a mechanism to prevent bone loss during hibernation. This study willexplore the cellular mechanism behind bone maintenance in hibernating bears.1.2 Basics of bone remodelingBone is a dynamic organ which responds to a complex array of endocrine,neural, and mechanosensory stimulation by adapting its structure metabolically [22, 23].The skeleton simultaneously serves two competing functions. Its first function is toprotect the internal organs and serve as a lever arm for locomotion. Bone must thereforebe strong and stiff, and it must respond to mechanical loading by remodeling itsstructure. Its second function is as a reservoir for minerals such as calcium, phosphorus,and magnesium. When serum levels decrease, bone must release these minerals bybreaking down (and therefore weakening) its structural integrity. Bone is thereforesubject to continuous remodeling such that most of the adult skeleton is recycled every10 years. This remodeling is under the intricate control of three basic cell types.Osteoblasts are the bone forming cells. They are derived from mesenchymal stem cellslocated in the bone marrow. Following breakdown of bone, osteoblasts line the surfaceof the resorption cavity and begin pumping out new organic matrix and proteins whichpromote mineralization. As new bone is formed, some osteoblasts are trapped inside thematrix. These cells terminally differentiate into osteocytes, which form long cytoplasmicprocesses connecting these cells to other osteocytes, osteoblasts, and bone lining cells[24]. These processes serve a mechanosensory function in bone [25]. The remainingosteoblasts either undergo apoptosis or become quiescent bone lining cells, which forma barrier between the bone surface and osteoclasts. Upon activation of resorption, bonelining cells retreat from the bone surface, leaving an unprotected surface for osteoclastattachment [26]. Osteoclasts serve as the bone macrophage. Upon signaling fromosteoblasts and osteocytes, hematopoietic stem cells terminally differentiate intomultinucleated osteoclasts, which tightly glom to naked bone surfaces, creating aquarantined resorption cavity [27]. The osteoclast then releases acid and proteaseswhich disintegrate the mineral and cleave the organic matrix [28]. This process isreferred to as the activation and resorption phases of bone remodeling. It is followed bythe reversal and formation phases [29]. Bone resorption and formation are thus coupled,ensuring that wherever bone is resorbed, new bone replaces it [30].2