Installing and thereafter removing an aberrant prosthesis elicited opposite remodelling responses in growing mouse temporomandibular joints

Abstract

Temporomandibular joint (TMJ) displays a high remodelling capability. The current purpose was to investigate the differences between mandibular condylar remodelling responses of growing mice to installation and removal of unilateral anterior crossbite (UAC) prosthesis. Twenty-four mice were divided into one mock control group and two UAC groups. Unilateral anterior crossbite was created by installing a pair of prosthesis to left-side maxillary and mandibular incisors. Unilateral anterior crossbite was removed in removal group at 3 weeks but remained in UAC group. Temporomandibular joints were sampled at 7 weeks. Changes in condylar cartilage and subchondral bone were assessed by histology and in vivo micro-CT. Real-time PCR and immunohistochemistry were performed to evaluate expression changes in ADAMTS-5, MMP-3, MMP-9, MMP-13, IL-1, TNF-α, OPG and RANKL. Statistical analysis was performed at α = 0.05. Temporomandibular joint cartilage degradation was induced by UAC as previously reported but was reversed by removal of UAC. The dropped cartilage thickness, chondrocyte number and collagen II-positive area, the increased expression levels of Adamts-5, Mmp3, 9, 13, Tnf-α and Il-1β in cartilage, the decreased ratio of OPG/RANKL in both condylar cartilage and subchondral bone, the loss of TMJ subchondral bone and the increase in the TRAP-positive cells in subchondral bone were all reversed in the removal group (P < 0.05). The growing mouse TMJ condyle displays a high remodelling capability which can be degenerative and rehabilitative, respectively, in response to placement and thereafter removal of the aberrant prosthesis. Eliminating aberrant prosthesis is helpful to promote the degraded condyle to recover.

Molecular changes in peripheral blood involving osteoarthritic joint remodelling

“…Based on a gene array analysis, Appleton et al indicated that the gene expression changes in a surgically developed rat OA model were similar to those found in human OA . Recently, we developed a prosthetic unilateral anterior crossbite (UAC) rodent model in which typical OA‐like lesions were observed in TMJs, such as chondrocyte death, cartilage matrix loss, osteochondral interface stiffening and abnormal reparative bone turnover . In the present study, we first detected molecular changes in the PBLs of UAC rats.…”

“…Osteoclasts can be directly activated by IL6; simultaneously, IL1 and TNF‐alpha upregulate RANKL on the surface of osteoblasts and/or stromal cells interacting with its cell surface receptor, RANK, on osteoclast precursors, resulting in increased numbers of osteoclasts . Our published data indicated that there was an increased expression of TNF‐alpha, together with the upregulated gene expression of IL1 and IL6, in the early stages of UAC‐treated rat and mouse TMJs . The UAC‐stimulated TNF‐alpha accelerated the chondrocyte apoptosis induced by UAC via the death‐receptor pathway .…”

“…32 Our published data indicated that there was an increased expression of TNF-alpha, together with the upregulated gene expression of IL1 and IL6, in the early stages of UACtreated rat and mouse TMJs. 17,35 The UAC-stimulated TNF-alpha accelerated the chondrocyte apoptosis induced by UAC via the death-receptor pathway. 35 However, in this long-term study, according to the microarray assay, the downregulated fold changes of TNF-alpha, IL1 and IL6 were 2.5, 1.4 and 1.5 times greater in the UAC_Gene group, respectively, than in the Con_Gene group.…”

“…13 Recently, we developed a prosthetic unilateral anterior crossbite (UAC) rodent model in which typical OA-like lesions were observed in TMJs, such as chondrocyte death, cartilage matrix loss, osteochondral interface stiffening and abnormal reparative bone turnover. [14][15][16][17][18] In the present study, we first detected molecular changes in the PBLs of UAC rats. We then described the significance of the molecular changes disclosed in the PBLs of the UAC rats in the related tissues, including the alveolar bone, TMJ disc, mandibular condylar cartilage and subchondral bone.…”

Early growth response 1 reduction in peripheral blood involving condylar subchondral bone loss

“…Recently, we developed a TMJ OA rodent model by installing an aberrant prosthesis to create a unilateral anterior crossbite (UAC) condition. The induced TMJ OA changes included cartilage degradation, subchondral bone loss as revealed by micro‐CT and altered expression levels of molecular markers (Jiao et al, ; Lu et al, ; Wang et al, ; Yang et al, ; Yang, Zhang, et al, ; Zhang et al, , ). Our recent work indicated that the mRNA expression of Egr1 in peripheral blood leucocytes (PBLs) was increased after 20 weeks of UAC stimulation (Zhang et al, ) at which stage condyle was deformed (Zhang et al, ).…”