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?2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

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 ?-adrenergic receptors (?-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 ?-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and ?2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. ?-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while ?-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of ?2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of ?2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that ?2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.

SUBMITTER: Jiao K

PROVIDER: S-EPMC4518212 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

Jiao Kai K Niu Li-Na LN Li Qi-hong QH Ren Gao-tong GT Zhao Chang-ming CM Liu Yun-dong YD Tay Franklin R FR Wang Mei-qing MQ

Scientific reports 20150729

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 subchondra ...[more]

PMID: 26219508

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Project description:Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl expression, in which JNK and/or Ca(2+)/NFAT pathways were involved and therefore were engaged in enhancing the migration and differentiation of osteoclast precursors, leading to increased osteoclast activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated rats.

Dataset Information

?2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

Publications

β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

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