Role of osteoclasts in oral homeostasis and jawbone diseases

Abstract

The jawbone is a unique structure as it serves multiple functions in mastication. Given the fact that the jawbone is remodeled faster than other skeletal bones, bone cells in the jawbone may respond differently to local and systemic cues to regulate bone remodeling and adaptation. Osteoclasts are bone cells responsible for removing old bone, playing an essential role in bone remodeling. Although bone resorption by osteoclasts is required for dental tissue development, homeostasis and repair, excessive osteoclast activity is associated with oral skeletal diseases such as periodontitis. In addition, antiresorptive medications used to prevent bone homeostasis of tumors can cause osteonecrosis of the jaws that is a major concern to the dentist. Therefore, understanding of the role of osteoclasts in oral homeostasis under physiological and pathological conditions leads to better targeted therapeutic options for skeletal diseases to maintain patients' oral health. Here, we highlight the unique features of the jawbone compared to the long bone and the involvement of osteoclasts in the jawbone-specific diseases.

Keywords: bone remodeling; jawbone; mechanical stress; osteoclast; osteonecrosis.

FIGURE 1

Mandibular development. A, The body of the mandible (white) formed lateral to Meckel's cartilage (blue) undergoes intramembranous ossification. The center of ossification (orange) is lateral to Meckel's cartilage at the bifurcation of the inferior alveolar nerve (yellow). B, The condylar process and a part of the coronoid process, the mental protuberance, and the mandibular angle are formed via endochondral ossification (green). These cartilages are called secondary cartilage

FIGURE 2

Bone resorption by osteoclasts. Bone-resorbing osteoclasts form ruffled borders and sealing zones to make the resorption lacuna acidic. Vacuolar H⁺-ATPase localized to the ruffled border transports protons into the resorption lacuna, while the chloride channel balances the ionic charge by transporting chloride simultaneously. Enzymes such as cathepsin K (CatK) and TRAP are secreted into the resorption lacuna to degrade bone matrix. Matrix degradation products are endocytosed from the ruffled border and released from the functional secretory domain

FIGURE 3

Coupling mechanism between osteoclasts and osteoblasts. Osteoblasts express RANK ligand (RANKL) and osteoprotegerin (OPG). RANKL binds to the RANK receptor, which is expressed on the surface of osteoclast precursors. RANKL binding to RANK receptor leads to differentiation and activation of osteoclasts. OPG acts as a decoy receptor for RANKL, thus preventing the RANK and RANKL interactions. Osteoclasts regulate migration and activity of osteoblasts through several mechanisms: (a) factors released from the bone matrix during bone resorption (yellow), (b) factors secreted from osteoclasts (red), and (c) direct interaction between osteoclasts and osteoblasts (blue)

FIGURE 4

Mechanical loading and bone remodeling. Increased mechanical loading reduces sclerostin production from osteocytes. Sclerostin inhibits osteoblast differentiation and stimulates osteoclastogenesis at least in part by upregulation of RANKL/OPG expression. The constant mechanical loading during mastication inhibits sclerostin production from osteocytes, which may decrease bone resorption and accelerate new bone formation in the jawbone

FIGURE 5

Tooth eruption and tooth movement. A, The levels of RANKL/OPG and M-CSF in the dental follicle are critical for tooth eruption. Bone resorption by osteoclasts at the coronal half of the dental follicle is required to widen a gubernacular canal to create the eruption pathway. New bone formation by osteoblasts at the base of the bony crypt is important for producing an outward eruption force directed against the erupting tooth. B, During orthodontic tooth movement, osteoclasts resorb bone matrix at the compressed side to create space for tooth movement, while new bone formation occurs at the tension side. RANKL, OPG, and prostaglandin (PG)E2 secreted from periodontal ligament (PDL) cells or osteocytes in response to mechanical stimuli control bone resorption

FIGURE 6

Regulation of bone resorption in periodontal disease. Lipopolysaccharide (LPS) originates from bacteria in the oral biofilm. LPS initiates osteoclastogenesis upon binding toll-like receptor (TLR) that is expressed on dendritic cells, macrophages, monocytes, osteoblasts, PDL cells, and gingival fibroblasts. Osteoblasts produce RANKL in response to LPS stimulation. RANKL and TNF-α secretion by B cells and T cells are induced by TNF-α produced by dendritic cells, macrophages and monocytes. Osteoclast differentiation is enhanced either by continuous exposure to RANKL, TNF-α, or both, while OPG secreted form gingival fibroblasts and PDL cells inhibit osteoclast differentiation. The direct interaction of LPS with preosteoclasts through TLR also promotes osteoclast differentiation