Loss of Occlusion Accelerates Condylar Degeneration in SAMP8 Mice

Objectives: Temporomandibular joint (TMJ) osteoarthritis (OA) is mainly caused by aging or occlusal abnormalities, including loss of occlusion. However, the mechanism underlying early-stage TMJ-OA and its progression remain to be clarified. We investigated molecular change and immunohistochemical localization in condylar cartilage and subchondral bone accompanying loss of occlusion in senescence-accelerated mouse (SAM).

Methods: Two 4-month-old strains were used: senescence-accelerated prone (SAMP8) mice and senescence-accelerated resistant (SAMR1) mice as a control, each strain comprising 40 males. Each strain was divided into two groups: a milling group (MG; crowns of upper and lower bilateral molars and incisors milled to loss of occlusion and soft dough diet for 2-8 weeks) and a non-milling group (NG; no molar or incisor milling and hard pellet diet for 2-8 weeks). The mandibular condyle was evaluated by immunohistochemistry and gene expression by real time polymerase chain reaction (RT-PCR) and in situ hybridization.

Results: In the MG group, immunohistochemistry revealed a reduction in type II collagen (Col II) and an increase in matrix metalloproteinase (MMP)-13 in condylar cartilage in both groups, while RT-PCR and in situ hybridization showed a reduction in gene expression of Col II, Aggrecan and Indian hedgehog (Ihh), and a gradual increase in gene expression of MMP-13 over 2-8 weeks compared with in the NG group. Although a significant reduction was observed in gene expression of type I collagen, Col II, Aggrecan, Ihh and Patched1 (Ihh receptor) in the SAMP8 MG group compared with in the SAMR1 MG group over 2-8 weeks, a significant increase was seen in gene expression of MMP13.

Conclusions: The results suggest that loss of occlusion affects extracellular matrix remodeling, leading to degradation of the mandibular condyle; that early degenerative SAMP8 TMJ conditions involve disruption of Ihh signaling; and that occlusal dysfunction accelerates progression of degenerative morbidity.