5c). In contrast, the condyle did not grow in the superior direction, but in an almost posterior direction. When the condylar cartilage is destroyed, as in this case, endochondral ossification, which provides the condyle with growth ability to resist against GPCR Compound Library chemical structure compressive forces exerted on it [11], [17] and [26], is disturbed. As a result, the condyle cannot grow in the superior direction, and compensatory posterior growth due to intramembranous ossification at the posterior condylar margin becomes predominant, which is one characteristic of the high-angle type [2] and [26].

These results suggest that the balance between intramembranous and endochondral ossification in the condyle may be a factor determining divergent condylar growth direction. Primary cartilage, such as articular cartilage and growth plates in a long bone, synchondroses in the cranial base, and nasal septal cartilage, consists of a chondrocyte NLG919 population (Fig. 6). In contrast, condylar cartilage (i.e., secondary cartilage) is a heterogeneous tissue containing cells at various stages of chondrogenic maturation [31], [32], [33], [34], [35], [36], [37], [38], [39], [40] and [41] (Fig. 7). Classifications and

terminology related to condylar cartilage cell layers differ among investigators (Table 1). Cell layer classification depends on animal species and growth stage, histological method, and molecular markers used in a given study. In this paper, a classification comprising four cell layers is used to explain the characteristics

of each cell layer because four cell layers can be easily distinguished from each other based on type I and II collagen localization. The most superficial layer of the condylar cartilage consists of dense fibrous connective 4-Aminobutyrate aminotransferase tissue with scattered cells, and its periphery is continuous with the outer layer of the periosteum (Fig. 7). The cells are flat and surrounded by dense collagen bundles [38], [39] and [40]. This layer is not related to deeper chondrogenic differentiation, but functions as a protective covering for the underlying cartilaginous tissue [38]. Recently, Ohno et al. [42] revealed that superficial zone protein, also known as proteoglycan-4 and lubricant, is restricted to the superficial part of the condylar cartilage and functions as a joint boundary lubricant. Based on cellular morphology, this layer is further divided into two sublayers: the upper sublayer (i.e., polymorphic cell layer), where irregular polygonal cells with large round nuclei are densely packed; and the lower sublayer (i.e., flattened cell layer), where flattened cells are oriented with their long axes parallel to the articular surface [38] (Fig. 7). The cells in the upper sublayer have poorly developed cytoplasmic organelles, extend thin cell processes to the adjacent cells, and form gap junctions [38].