The Mandibular Cartilage Metabolism is Altered by Damaged Subchondral Bone from Traumatic Impact Loading

Abstract

Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a degenerative disease caused by excessive external loading. Recently, it was reported that the damage in the mineralized subchondral bone caused by traumatic impact-loading is responsible for the initiation and progression of cartilage degeneration. Thus far, we have hypothesized that cytokines released from damaged subchondral bone from impact-loading affect the cartilage catabolism under pathological conditions. An impactor of 200 gw was dropped onto the top of a porcine mandibular condyle. After organ culture for 2 days, we investigated the association between the subchondral bone and cartilage using histological and biochemical experiments. The impact-loading induced the expression of IL-1beta immunohistochemically and prominently up-regulated IL-1alpha and IL-1beta mRNA levels in subchondral bone. We confirmed a significant decrease in type II collagen and aggrecan mRNA expressions in chondrocytes by co-culture with osteoblasts after impact-loading, and significant increase in mRNA and protein expressions of IL-1beta in subchondral osteoblasts from impact-loaded subchondral bone. The mRNA expressions of type II collagen, aggrecan, and type X collagen in chondrocytes were decreased significantly by the co-culture with osteoblasts pre-treated by IL-1beta, -6, and TNF-alpha. Among them, osteoblasts pre-treated by IL-1beta affected chondrocytes most strongly. It was also shown that IL-1beta-treated osteoblasts enhanced the MMP-1 mRNA level most markedly in chondrocytes among the four cytokines. These results suggest that the TMJ subjected to impact-loading can increase directly IL-1beta synthesis in the subchondral region, subsequently altering the metabolism of adjacent cartilage and may eventually resulting in the onset and progression of TMJ-OA.

Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co‐culture system

“…More interestingly, when co‐cultured with stressed chondrocytes or osteoblasts, the expression of type II collagen, aggrecan , and SOX‐9 mRNAs in chondrocytes was markedly lower than when chondrocytes were co‐cultured with unstressed chondrocytes or osteoblasts, respectively. These results were very similar to those reported in previous studies (28, 30, 31). Therefore, soluble mediators secreted from the co‐cultured osteoblasts could suppress chondrocyte‐specific markers (30, 31), and in another previous report, GAG synthesis in chondrocytes was significantly reduced in a model in which chondrocytes and osteoblasts were co‐cultured together in direct physical contact (28).…”

“…Furthermore, it is of great interest that microcracks in the subchondral mineralized tissue caused by overloading can contribute to the initiation of vascular invasion into the articular cartilage (27), which indicates a possible way in which cytokines may be trafficked, and may subsequently lead to the degeneration of cartilage. As for the mandibular condyle, it was reported that external loading, such as a traumatic impact, induced serious damage in the boundary layer between cartilage and subchondral bone (28). From these considerations, subchondral bone may play a crucial role in OA pathogenesis following either biomechanical or biological pertubations.…”

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

“…Swine models are currently being used in multiple medical and surgical disciplines, [33][34][35][36] suggesting that swine models as a proxy for human conditions are reasonable. Further benefits to the use of swine, include recent completion of the swine genome project, with steady increases in the number of swine transgenic models, 37,38 including a green fluorescent protein model 39 and a severe combined immunodeficiency model 40 ; these models yield exciting possibilities for preclinical trials in swine that were previously limited to rodent and primate models.…”

“…37,[41][42][43] Anatomic similarities between swine and humans in body size, maxillary bone anatomy, TMJ function 23 ; bone remodeling, regeneration, and cortical bone mineralization, and critical-sized bone defects, 44 also suggest that swine craniofacial models that mimic human conditions are also appropriate. Several swine models exist for use in craniofacial conditions including mandibular reconstruction, 33 post traumatic conditions, 36 cranial defects, 35 and nasal and Because weight significantly varied for 5-week-old piglets, a normalized defect size was established. Normalization was weight based, and created based on the knowledge that the 2 cm defect in a pig weighing 10.8 kg did not heal.…”

Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model

“…In fact, the actual cartilage layer in an explant is 1–2 mm. More, the development of osteoarthritis has been demonstrated after impact on the subchondral bone, without affecting the cartilage surface (Donohue et al, 1983; Lahm et al, 2004, 2006; Lin et al, 2009). Incorporating the different physical properties of bone and different cartilage layers will alter the stress/strain fields that are used as impact input and, along with the biochemical effect of trauma to the subchondral bone, is the subject of future work.…”