Abstract
The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.
Highlights
Increased subchondral bone remodeling have been observed in the early stages of OA5,6
Using a rat temporomandibular joint (TMJ) OA model, the present study provides novel insights to this issue by demonstrating that the sympathetic tone is activated in the condylar subchondral bone by iatrogenically-created abnormal occlusion
This is evidenced by increased level of bone norepinephrine, increased sprouting of tyrosine hydroxylase-positive sympathetic nerve fibers, and increased expression of β 2-adrenergic receptors (Adrb2) at the gene and protein levels in the condylar subchondral bone
Summary
Increased subchondral bone remodeling have been observed in the early stages of OA5,6. Mesenchymal stem cells (MSCs) derived from bone marrow is the progenitor cell of osteoblasts They secret cytokines such as receptor activator of nuclear factor kappa-β ligand (RANKL) and osteoprotegerin (OPG) to modulate the development of osteoclasts from their precursors. The present study was conducted to bridge these knowledge gaps by testing the hypothesis that activation of the sympathetic tone induced by aberrant joint loading elicits osteoclast-mediated subchondral bone remodeling in a rat TMJOA model. To address this hypothesis, abnormal dental occlusion was created in experimental rats to examine whether abnormal occlusion activates sympathetic tone in condylar subchondral bone, and whether inhibition of β -adrenergic signals prevents condylar subchondral bone loss. The pro-osteoclastic effects induced by norepinephrine stimulation of MSCs were further examined to understand the underlying mechanism responsible for norepinephrine-induced bone resorption
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