Injecting vascular endothelial growth factor into the temporomandibular joint induces osteoarthritis in mice

Abstract

It is unclear whether vascular endothelial growth factor (VEGF) can initiate osteoarthritis (OA) in the temporomandibular joint (TMJ). In this study we evaluated the effects of intra-articular injection of exogenous VEGF in the TMJ in mice on the early stage. Forty-eight male Sprague-Dawley mice were equally divided into 3 groups. In the vegf group, the mice received an injection of VEGF solution (50 μL) in the TMJ once a week over a period of 4 weeks. In the sham group, the mice received an injection of saline (50 μL). The control group did not receive any injection. Four mice from each group were sacrificed at 1, 2, 4, and 8 weeks. Gradual prominent cartilage degeneration was observed in the vegf group. Additionally, this group showed higher expressions of metalloproteinase (MMP)-9, MMP-13, receptor activator of nuclear factor-kappa-B ligand (RANKL), and a higher number of apoptotic chondrocytes and VEGF receptor 2 (VEGFR2)-positive chondrocytes. Micro-computed tomography (CT) revealed prominent subchondral bone resorption in the vegf group, with a high number of osteoclasts in the subchondral bone. In vitro study demonstrated that VEGF can promote osteoclast differentiation. In conclusion, our study found that VEGF can initiate TMJ OA by destroying cartilage and subchondral bone.

Masseter muscle atrophy impairs bone quality of the mandibular condyle but not the alveolar process early after induction

“…It still remains to be explored whether BoNTA intervention in the masseter muscle affects bone structure of the mandible even earlier than reported here. Since bone microstructure and morphology are relevant parameters for the evaluation of bone quality in general, our pre‐clinical study demonstrates that the mandibular condyle experiences similar consequences to those observed in articular and degenerative TMJ disorders, shared by humans and mice . Therefore, the safety of BoNTA treatment for pathologies that specifically affect the masseter muscle such as sleep bruxism and myofascial pain should be more critically evaluated in future studies.…”

Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain

“…Additionally, the condylar chondrocytes exhibited increased expression of nuclear factor‐kappa‐B ligand (RANKL), which suggests that chondrocytes are potential mediators of VEGF‐mediated subchondral bone resorption through stimulation of RANKL. The subchondral bone of VEGF‐treated joints showed a higher number of tartrate‐resistant acid phosphatase (TRAP) positive osteoclasts . In contrast to Ludin et al (2013), discontinuation of IA VEGF treatment did not lead to resolution of subchondral bone pathology at 4 weeks post‐administration.…”

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

“…In OA, VEGF has also been linked to vascular invasion in the normally avascular cartilage, recruiting osteoblasts that lay down new bone matrix and osteoclasts that degrade the cartilage matrix [54]. VEGF has been associated with stimulation of RANKL, which aids in osteoclastogenesis in the subchondral bone and in turn secretes more VEGF into the articular cartilage to stimulate proteolytic enzymes and pro-inflammatory cytokines [61]. In this study, we show procyanidins reduced the expression of VEGF and VEGF activator hypoxia-inducible factor (Hif)1-α [71], and inhibited phosphorylation of VEGFR-2, which plays a major role in mediating the effects of VEGF [72].…”

“…While the expression of VEGF is largely quiescent during maturity in adult non-OA cartilage, its expression is elevated in OA cartilage [56,57,58,59]. Furthermore, intra-articular injections of VEGF into the mouse knee joint [60] and the temporomandibular joint [61] induce OA, and intra-articular injections of VEGF-specific antibody bevacizumab mitigates OA progression in OA rabbits [62]. VEGF has also been demonstrated to regulate several pathways in OA pathogenesis, such as those involved in oxidative stress and catabolism [63].…”