Age-related changes in the cartilage of the temporomandibular joint

Abstract

Osteoarthritis (OA) of the knee is closely associated with aging; however, little is known about the age-related degeneration in the mandibular condylar cartilage (MCC) of the TMJ. Our objective was to examine whether a correlation exists between aging and degeneration of the MCC of the TMJ. Thirty-two male C57BL/6J wild-type mice were aged to 2, 12, 18, and 25 months old. The mice were euthanized by CO 2 inhalation and were dissected and examined by micro-CT and histology. Sagittal sections of the condyles were stained for tartrate-resistant alkaline phosphatase, alkaline phosphatase, safranin O, picrosirius red, and toluidine blue. In addition, immunostaining for BMP2, BMP4, BMP7, PRG4, and MMP13 was performed. Bone volume fraction and tissue density significantly increased with the age of the animals. There was a significant increase in the Osteoarthritis Research Society International histopathological score and mineralization of the noncalcified cartilage in the aged animals. There was a decrease in cartilage thickness, proteoglycan distribution, and cellularity in the aged animals. Additionally, we noted increased picrosirius red staining with the increase in the age of the animals. Our protein expression showed increased BMP2, BMP4, BMP7, and MMP13, whereas there was a decrease in PRG4 expression in the aged animals. As the animal ages, there is decreased proteoglycan secretion, decreased cellularity, decreased cartilage thickness, increased fibrillation, and increased proteolytic activity. A better understanding of the basic mechanisms underlying the degeneration of the MCC in the older animals could provide novel ways to slow the development of OA.

Senolytics alleviate the degenerative disorders of temporomandibular joint in old age

“…It is still unclear how D+Q increases cartilage thickness and bone turnover (increased AP and TRAP signals) in old TMJs. We found that Bmp2 level increased with aging (consistent with previous findings (Chen et al, 2020)), while DQ has little effect on Bmp2 level in either young or old TMJs (Figure 1a), indicating that D+Q might not work through Bmp2 pathway. Future experiments are needed to further investigate these underlying mechanisms.…”

“…Notably, we observed that D+Q increased cartilage thickness by more than 30% in old TMJs within 5–8 weeks (Figure 2b). Since TMJ cartilage thickness declines gradually with aging (Chen et al, 2020), our data support less degeneration with DQ treatment and plausible reasons could be regeneration or prevention of degeneration of the TMJ cartilage. This could be clinically significant, since the current barrier to success in TMJ degeneration treatment is that TMJs fail to regenerate the diseased cartilage tissue that could recapitulate the cellular composition, structure, and load‐bearing capacity of healthy joint cartilage.…”

“…Interestingly, we observed TRAP signal in MCC in D+Q‐treated old TMJs while the TRAP signal was limited to subchondral bone in all V‐treated old TMJs. Increased TRAP expression in MCC is also observed in young TMJs (Chen et al, 2020; Dutra et al, 2018) and may be related to the increased remodeling of the MCC, which is a hallmark of young TMJs. These data suggest that intermittent administration of D+Q can improve bone turnover (both bone formation and resorption) in old TMJs.…”

“…Similar to other aged tissues, D+Q significantly reduced the p21 (a key cellular senescence marker), Rela (v‐rel avian reticuloendotheliosis viral oncogene homolog A, a key subunit for NF‐κB pathway) and senescence‐related matrix metalloproteinase 13 (Mmp13) levels (Jeon et al, 2017; Wang et al, 2020) in old TMJs (Figure 1a and Figure ), demonstrating the efficacy of these senolytics. We first performed histomorphometric analysis (Chen et al, 2020) on these TMJs. The MCC of the TMJ consists of both mineralized cartilage and non‐mineralized cartilage (Bonnevie & Mauck, 2018; Utreja et al, 2016).…”

“…The prevalence of TMJ degeneration is high in the older population, with a prevalence of 45%-70% in individuals over 65 (Schmitter et al, 2010). With aging, progressive loss of structure, function, coordination, and physiological integrity occurs in the mandibular condylar cartilage (MCC) and the subchondral bone of the TMJ, leading to TMJ degeneration (Chen et al, 2020). Degenerative disorders of the TMJ can cause severe pain, joint immobility, and compromised quality of life in patients (Trize et al, 2018), especially in older population with reduced resilience.…”