Radiological trace of mandibular primary growth center in postnatal human mandibles.код для вставкиСкачать
THE ANATOMICAL RECORD PART A 288A:1234–1242 (2006) Radiological Trace of Mandibular Primary Growth Center in Postnatal Human Mandibles YOUNG JOON LEE,1 SANG SHIN LEE,1 BYOUNG GEOL PARK,1 SANG DOO WOO,1 EUN CHEOL KIM,2 YEON SOOK KIM,1 SUK KEUN LEE,1* AND JE GEUN CHI3 1 Department of Oral Pathology, College of Dentistry, Kangnung National University, Gangneung, Korea 2 Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Korea 3 Department of Pathology, College of Medicine, Seoul National University, Seoul, Korea ABSTRACT The mandibular primary growth center (MdPGC) of human fetus was conspicuously deﬁned in the soft X-ray view of fetal mandibles. As the peripheral adaptive growth of mandible advances during the postnatal period, the MdPGC image became overshadowed by condensed cortical bones in soft X-ray view. In this study, we traced a sclerotic sequela of MdPGC during the postnatal period. Panoramic radiograms of 200 adults and soft X-ray views of 30 dried adult mandibles were analyzed by statistical methods. The former clearly showed an MdPGC below the middle portion of apices of canine and ﬁrst premolar, which was distinguishable from mental foramen, and the latter also showed the MdPGC at the same area as a radiating and condensed radiopaque image, measuring 0.5–1.0 cm in diameter. This MdPGC position was seldom changed in the elderly people, even in the edentulous mandibles. Additionally, in the radiological examination, the benign tumors including odontogenic cysts hardly involved the MdPGC, while the malignant tumors of both primary and metastatic cancer frequently destroyed the MdPGC. Anat Rec Part A, 288A:1234–1242, 2006. Ó 2006 Wiley-Liss, Inc. Key words: mandibular primary growth center; postnatal period; pantomogram; dried adult mandible The mandible consists of a unique bony structure with tight attachment of strong masticatory muscles and delicate facial expression muscles and develops a joint with temporal bone, resulting in temporomandibular joint (Haskell, 1979; Bresin et al., 1999; Tumer and Gultan, 1999; Bresin, 2001). Although it is well known that the whole mandibular structure is derived from the ﬁrst branchial arch, yet the prenatal development of mandible is one of the debating subjects for the morphogenesis of orofacial structure (Hall, 1982; Lee et al., 1990, 1996, 2001; Barni et al., 1998). The Meckel’s cartilage may play an important role in the topographical organization and in the differentiation of the facial structure during the embryonal and early fetal period (Plessis et al., 1991; Orliaguet et al., 1994; MacDonald and Hall, 2001; Radlanski et al., 2003; Lorentowicz-Zagalak et al., 2005). Ó 2006 WILEY-LISS, INC. The initiating role played by the ventral part of Meckel’s cartilage on the ossiﬁcation of mandible during the embryonal period leads to the formation of the mandibular primary growth center (MdPGC). The partial ﬁbrous evolu- Grant sponsor: Korean Science and Engineering Foundation; Grant numbers: R11-2002-097-07004-0 and R01-2003-000-10891-0. *Correspondence to: Suk Keun Lee, Department of Oral Pathology, College of Dentistry, Kangnung National University, Gangneung 210-702, Korea. Fax: 033-642-6410. E-mail: email@example.com Received 26 April 2006; Accepted 21 July 2006 DOI 10.1002/ar.a.20392 Published online 19 October 2006 in Wiley InterScience (www. interscience.wiley.com). MANDIBULAR PRIMARY GROWTH CENTER tion and the regression of the major part of the ventral branch of Meckel’s cartilage start only after 16 weeks of intrauterine life (Bontemps et al., 2001). Bone growth of the fetal mandible is a complex process comprising lingual resorption and buccal apposition, and resting the ossiﬁcation areas seamed by lining cells (Radlanski et al., 1999; Radlanski and Klarkowski, 2001). Later growth of mandible is easily observed in the condyle head and symphysis suture, but it is still hard to explain the morphogenetic development of whole mandible by the condyle and symphysis growth only. In a previous study, we determined the MdPGC in human fetuses. The MdPGC has an important morphogenetic effect for the development of the human mandible, providing a growth center for the trabecular bone of mandibular body and also indicating the initial growth of endochondral ossiﬁcation of the condyle (Lee et al., 2001). From these series of results, one MdPGC was observed below the middle portion of apices of canine and ﬁrst premolar, a little anteriorly located to the mental foramen in soft X-ray view of the removed fetal mandibles. And the MdPGC was the most active site for mandible body formation during fetal period by the participation of the intramembranous bone ossiﬁcation along the radiating trabeculae to form the mandibular body, including mandibular angle, coronoid process, symphysis, and alveolar bone, while condyle head was also active for condyle growth by endochondral ossiﬁcation (Kjaer, 1978; Baumrind et al., 1983; Morimoto et al., 1987; Orliaguet et al., 1993b; Eroz et al., 2000; Lee et al., 2001). The aim of this study was to deﬁne the sequela of the MdPGC in the postnatal adult mandibles by radiological method, and we found a focal radiopaque image in the anterior mandibular body that was clearly distinguishable from the radiological images of mental foramen and lingual torus. Through the statistical analysis for the positional measurements of the radiopaque spot during the postnatal life, we determine this radiopaque spot is identical to the sequela of MdPGC and discuss its roles for the postnatal growth of mandible. MATERIALS AND METHODS Two hundred cases of pantomograms were obtained from the patients, ranging from 11 to 79 years old, who visited for routine check at Kangnung National University Dental Hospital from 2002 to 2005, using X-ray machine of Cranex 3þ Ceph (Soredex Orion, Finland), and their images were digitalized by FCR 5000 (Fuji Medical System, Japan). All materials were legally approved by Kangnung National University Dental Hospital and Dental College. The pantomograms were taken in ordinary head position indicated by the X-ray machine protocol and analyzed for the position of MdPGC and mental foramen in mandibular body by measuring their proportional dimensions of horizontal and vertical positions. The horizontal ratios of MdPGC and mental foramen were measured by the ratio of symphysis-MdPGC/symphysis-mandibular angle, and symphysis-mental foramen/symphysis-mandibular angle, respectively. The symphysis-mandibular angle is identical to the mandibular body length. And the vertical ratios of MdPGC and mental foramen were measured by the ratio of inferior mandibular border- 1235 MdPGC/inferior mandibular border-superior margin of alveolar bone, and inferior mandibular border-mental foramen/inferior mandibular border-superior margin of alveolar bone, respectively. The length between inferior mandibular border and superior margin of alveolar bone is identical to the mandibular body height. The positions of MdPGC and mental foramen, obtained from 11- to 79year-old subjects, were plotted to elucidate the growth pattern (Fig. 1). Thirty dried adult mandibles were the materials preserved for anatomical teaching. Their use was approved by the human tissue committee of Kangnung National University. They were examined by soft X-ray (ﬁlm, Fuji, Tokyo, Japan) using Faxitron machine (Hewlett-Packard, Corvallis, OR). The radiograms were analyzed to deﬁne the radiopaque image of MdPGC in adult mandibles. Additionally, in order to evaluate the rigidity of MdPGC in pathological conditions, 30 cases of benign and malignant tumors involving the anterior mandibular body were selected and examined for the morphological changes of radiopaque image of MdPGC on pantomogram. RESULTS Pantomograms of Adult Human Mandibles A focally condensed radiopaque image was observed bilaterally in the anterior mandibular body on the wellprocessed pantomograms, and it usually appeared as a round shape with radiating pattern below the middle portion of apices of canine and ﬁrst premolar. It measured 0.5–1.0 cm in diameter. This radiopacity was clearly distinguishable from mental foramen, which also located more distally, and also from the lingual torus, which was usually located more mesially and showed round homogeneous radiopacity (Fig. 4). From 200 pantomograms, the position of the radiological images of MdPGC and mental foramen were evaluated. The proportional ratios of MdPGC and mental foramen in the mandibular body were compared. The horizontal ratio of MdPGC gradually decreased from 0.25 to 0.18 during the postnatal age, while the horizontal ratio of mental foramen gradually increased from 0.24 to 0.41 (Fig. 2A and B). The average horizontal ratio of MdPGC was 0.22 6 0.034, and the average vertical ratio of MdPGC was 0.37 6 0.061, while the average horizontal ratio of mental foramen was 0.3 6 0.034 and the average vertical ratio of mental foramen was 0.36 6 0.082 (Table 1). However, the positions of both MdPGC and mental foramen were stable, and they were separately observed far apart as different osseous trabecular pattern on the pantomograms. The distance between MdPGC and mental foramen remained stable during the postnatal period, and its average was 9.4 6 1.56 mm (Fig. 2C). Soft X-Ray View of Dried Adult Mandibles In the soft X-ray view of 30 dried adult mandibles, the focal condensed radiopaque area could be seen in the same area seen on the pantomograms of adults. The radiopacity showed a radiating trabecular pattern, below the middle portion of apices of canine and ﬁrst premolar, and measured between 0.5 and 1.0 cm in diameter. The 1236 LEE ET AL. Fig. 1. Schematic presentation of human mandible for the measurements of horizontal and vertical positions of MdPGC and mental foramen on the pantomogram. MBL, mandibular body length; MBH, mandibular body height; Xn, mandibular horizontal length from symphysis; Yn, mandibular vertical length from inferior border of mandibular body. mental foramen and inferior alveolar canal were separately observed in the anterior mandibular body (Fig. 3). MdPGCs in Pathological Changes by Benign and Malignant Tumors Pantomograms with both benign and malignant lesions were evaluated. Pantomograms with different benign lesions, i.e., ﬁbrous dysplasia (n ¼ 3), traumatic bone cyst (n ¼ 2), odontogenic ﬁbroma (n ¼ 3), and odontogenic myxoma (n ¼ 2), showed distinctive MdPGCs. There was no case of destruction or resolution of the MdPGC image. However, The MdPGCs were slightly displaced in two cases of odontogenic ﬁbroma. Ten cases of odontogenic cysts involving the anterior mandibular body area showed stable MdPGCs, although some MdPGCs were slightly displaced in three cases of odontogenic keratocyst. On the other hand, malignant lesions, i.e., oral squamous cell carcinoma (n ¼ 7) and metastatic cancer (n ¼ 3), showed severe destruction of radiopaque image of MdPGC by the tumor growth (Fig. 5). DISCUSSION The basic growth pattern of the mandibular body and condyle appears in the 7th week of fertilization. Histologically, the embryonal mandible is originated from pri- mary intramembranous ossiﬁcation in the ﬁbrous mesenchymal tissue around the Meckel’s cartilage. From this initial ossiﬁcation, the ramifying trabecular bones develop forward, backward, and upward to form the symphysis, mandibular angle, and coronoid process of the mandible, respectively (Lee et al., 2001). Although the ossiﬁcation is affected by complicated factors of endogeneous and exogeneous origins (Morimoto et al., 1987; Merida-Velasco et al., 1993, 1999; Orliaguet et al., 1993a, 1993b, 1994; Bach-Petersen et al., 1994; Ishizeki et al., 1999), the embryonal bones are primarily deposited by intramembranous ossiﬁcation initiated from the primary growth center (Pritchett, 1991; Rosati et al., 1994; Nyska et al., 1995). In the previous studies about prenatal maxillary and mandibular growth patterns, we observed the anterior and posterior maxillary primary growth centers (MxPGCs) and MdPGCs, which have characteristic radiating trabecular patterns both in the histological and radiological observations (Lee et al., 1992, 2001). We also mentioned that the MxPGC and MdPGC were embryonal initial ossifying sites of jaws, but they are neither continuously proliferative nor renewed during the late fetal and postnatal period. They rather remain as a sclerotic structure with the associated neurovascular tissues. Even though it was frequently insisted that there is no direct connection between the Meckel’s cartilage and embryonal mandible, many authors still believe that the Meckel’s cartilage, as a core cartilage of ﬁrst branchial MANDIBULAR PRIMARY GROWTH CENTER Fig. 2. Graphs for the measurements of horizontal and vertical positions of MdPGC and mental foramen during the postnatal period, ranging from 11 to 79 years. The horizontal ratio of MdPGC (symphysis-MdPGC/mandibular body length) gradually decreased, while the 1237 vertical ratio of MdPGC (inferior border-MdPGC/mandibular body height) gradually increased. However, the distance between MdPGC and mental foramen was relatively constant. 1238 LEE ET AL. TABLE 1. The average measurements for the position of MdPGC and mental foramen from 200 pantomograms used in this study Types MdPGC (X1, Y1) Mental foramen (X2, Y2) Ratio of Xn/mandibular body length* 0.22 6 0.034 0.3 6 0.034 y Ratio of Yn/mandibular body height** 0.37 6 0.061 0.36 6 0.082 *horizontal ratio. **vertical ratio. y unit; ratio (P < 0.005). The average distance between MdPGC and mental foramen: 9.4 6 1.56 mm (Fig. 2C). arch, plays some role to induce mandibular growth (Plessis et al., 1991; Yamasaki et al., 1991; Shum et al., 1993; Kjaer, 1997; Rodriguez-Vazquez et al., 1997a, 1997b; Trichilis and Wroblewski, 1997; Ishizeki et al., 1999). It was also reported that the Meckel’s cartilage is closely associated with the periosteum of the embryonal mandible, and that the genioglossus muscle is primarily attached to the Meckel’s cartilage and successively relocated its fusion into the ossifying mandible (Lee et al., 1990). But the direct histogenetic effect of Meckel’s cartilage for the mandibular development was frequently debated by many authors (Plessis et al., 1991; Orliaguet et al., 1994; Rodriguez-Vazquez et al., 1997b; Lee et al., 2001; Radlanski et al., 2003; Lorentowicz-Zagalak et al., 2005). In this study, we found that the MdPGC is produced by the intramembranous ossiﬁcation, and that it becomes the primary backbone of fetal mandible not affected by secondary appositional growth of bone by the tension of functional muscular forces. We also described that the MdPGC is a relatively rigid structure producing peripherally radiating trabeculae to form the basic mandibular structures, including symphysis, condyle, coronoid process, and alveolar bone. These ﬁndings lead us to explore the X-ray pantomograms of adults and soft X-ray views of dried adult mandibles preserved for the anatomical teaching. We found a focal condensed radiopacity, which was easily distinguishable from mental foramen and lingual torus. We think this condensed radiopacity is identical to the prenatal MdPGC found in the soft X-ray views of fetal mandibles. This radiopaque area could be correlated with the histological sections of the dried adult mandible, which diffusely showed sclerosed trabecular bony structure with numerous osteoporotic marrow spaces, but it was hard to deﬁne the spot of MdPGC. During the mixed dentition, from 7 to 12 years old, the focal condensed radiopacity was not well deﬁned on pantomogram due to overlapping with the crowded mixed dentition. Thereafter, as the mandibular body rapidly grew from the age of 15 years, the anterior mandibular body increased enough to show the radiopaque spot. Its trabecular pattern was clearly distinguishable from the surrounding mandibular bone. In the older-age group, the radiopaque image was gradually condensed in the anterior portion of mandible. These facts indicate that the focal condensed radiopacity of MdPGC may play a role for the maintenance of mandibular marrow structure during postnatal period. The gradual decrease of horizontal ratio of MdPGC during the postnatal period indicates the posterior mandibular body, which grows more backward to produce prominent mandibular angle. The gradual increase of vertical ratio of MdPGC indicates that the inferior border of mandible grows more downward than the alveolar bone, or else the alveolar bony height gradually decreased as a senile change in the elderly people. These ﬁndings may suggest that the mandibular body grows backward and downward in contrast to the forward and clockwise growth of condyle, and conversely when the condensed radiopaque spot is considered as a landmark of MdPGC and placed in the center of the mandibular body growth. It is easily demonstrated that the mandibular body can grow backward and downward to produce the prominent mandibular angle and inferior border of mandible, at which major masticatory and facial expression muscles are tightly attached. Therefore, we suppose that the condensed radiopaque spot in the anterior mandibular body is identical to the MdPGC of prenatal mandible and also plays a central role of mandibular body growth during the postnatal period. Particularly the mandible is associated with three different origins of muscle groups, i.e., masseter muscles originated from the ﬁrst branchial arch, facial expression muscles originated from the second branchial arch, and lingual muscles originated from the occipital myotome (Lee et al., 1996; Kuratani et al., 1999). Therefore, the development of mandible shows heterogeneous morphology, which has been a major debating topic (Maddox et al., 1998; Ishizeki et al., 1999; Tavakkoli-Jou et al., 1999; Mina, 2001a, 2001b; Wang et al., 2001). Because the muscular attachment affects the intramembranous osteogenesis, and the areas of future muscle attachment are sites of rapid bone formation throughout the early formative stages (Gaudino et al., 1995; Lee et al., 2001; Tan et al., 2002), we also suppose that the sequela of the MdPGC may persistently play a role for the growth of mandibular skeletal axis to support the mandibular movement induced by masticatory and facial musculatures. In the present study using 200 pantomograms and soft X-ray views of 30 dried adult mandibles, we observed a condensed radiopaque image, measuring 0.5–1.0 cm in diameter, below the middle portion of apices of canine and ﬁrst premolar. This radiopaque image was clearly distinguishable from the structures of mental foramen and lingual torus and showed a conspicuous radiating pattern. We supposed that it is a remnant of the MdPGC of prenatal mandible. However, the radiopaque area of MdPGC was seldom changed in the older person, even in the edentulous mandible. The odontogenic cysts and benign tumors hardly destroyed the original structure of MdPGC, while the primary or metastatic cancer rapidly destroyed the radiopaque area of MdPGC. MANDIBULAR PRIMARY GROWTH CENTER Fig. 3. Soft X-ray views of dried adult mandibles. Oblique lateral view showed the condensed radiopaque image with radiating trabecular pattern (arrows), which was separated from mental foramen (arrowhead). The MdPGC showed conspicuous trabecular pattern (A) or condensed radiopacity (B). 1239 1240 LEE ET AL. Fig. 4. Pantomograms of normal subjects. Every pantomogram showed the MdPGCs bilaterally in the anterior mandibular body (arrows). High magniﬁcation of the area of MdPGC was also shown in the square inlet at lower corner. MANDIBULAR PRIMARY GROWTH CENTER Fig. 5. Pantomograms of patients involved with different osseous lesions. A: The MdPGC areas (arrows) were well preserved even though the extensive swelling of periapical cyst (arrowheads) involved the whole lower anterior teeth. B: Fibrous dysplasia (arrowheads) involving the whole right mandibular body was extended near the MdPGC (arrows), but the radiopaque trabecular pattern was stable compared to 1241 the MdPGC in the left mandibular body (arrows). C: The inﬁltrative growth of squamous cell carcinoma (arrowheads) extensively destroyed not only the mandibular body but also the radiopaque image of MdPGC (arrows). High magniﬁcation of the area of MdPGC was also shown in the square inlet at lower corner. 1242 LEE ET AL. ACKNOWLEDGMENTS The authors thank the donors of human materials. LITERATURE CITED Bach-Petersen S, Kjaer I, Fischer-Hansen B. 1994. Prenatal development of the human osseous temporomandibular region. J Craniofac Genet Dev Biol 14:135–143. Barni T, Fantoni G, Gloria L, Maggi M, Peri A, Balsi E, Grappone C, Vannelli GB. 1998. Role of endothelin in the human craniofacial morphogenesis. J Craniofac Genet Dev Biol 18:183–194. Baumrind S, Korn EL, Isaacson RJ, West EE, Molthen R. 1983. Superimpositional assessment of treatment-associated changes in the temporomandibular joint and the mandibular symphysis. Am J Orthod 84:443–465. Bontemps C, Cannistra C, Hannecke V, Michel P, Fonzi L, Barbet JP. 2001. The ﬁrst appearance of Meckel’s cartilage in the fetus. Bull Group Int Rech Sci Stomatol Odontol 43:94–99. Bresin A, Kiliaridis S, Strid KG. 1999. Effect of masticatory function on the internal bone structure in the mandible of the growing rat. Eur J Oral Sci 107:35–44. Bresin A. 2001. Effects of masticatory muscle function and bite-raising on mandibular morphology in the growing rat. Swed Dent J (Suppl):1–49. Eroz UB, Ceylan I, Aydemir S. 2000. An investigation of mandibular morphology in subjects with different vertical facial growth patterns. Aust Orthod J 16:16–22. Gaudino G, Avantaggiato V, Follenzi A, Acampora D, Simeone A, Comoglio PM. 1995. The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene 11:2627–2637. Hall BK. 1982. Mandibular morphogenesis and craniofacial malformations. J Craniofac Genet Dev Biol 2:309–322. Haskell BS. 1979. The human chin and its relationship to mandibular morphology. Angle Orthod 49:153–166. Ishizeki K, Saito H, Shinagawa T, Fujiwara N, Nawa T. 1999. Histochemical and immunohistochemical analysis of the mechanism of calciﬁcation of Meckel’s cartilage during mandible development in rodents. J Anat 194:265–277. Kjaer I. 1978. Relation between symphyseal and condylar developmental stages in the human fetus. Scand J Dent Res 86:500–502. Kjaer I. 1997. Mandibular movements during elevation and fusion of palatal shelves evaluated from the course of Meckel’s cartilage. J Craniofac Genet Dev Biol 17:80–85. Kuratani S, Horigome N, Hirano S. 1999. Developmental morphology of the head mesoderm and reevaluation of segmental theories of the vertebrate head: evidence from embryos of an agnathan vertebrate, Lampetra japonica. Dev Biol 210:381–400. Lee SK, Lim CY, Chi JG. 1990. Development and growth of tongue in Korean Fetuses. Korean J Path 24:358–374. Lee SK, Kim YS, Lim CY, Chi JG. 1992. Prenatal growth pattern of the human maxilla. Acta Anat (Basel) 145:1–10. Lee SK, Kim YS, Jo YA, Seo JW, Chi JG. 1996. Prenatal development of cranial base in normal Korean fetuses. Anat Rec 246: 524–534. Lee SK, Kim YS, Oh HS, Yang KH, Kim EC, Chi JG. 2001. Prenatal development of the human mandible. Anat Rec 263:314–325. Lorentowicz-Zagalak M, Przystanska A, Wozniak W. 2005. The development of Meckel’s cartilage in staged human embryos during the 5th week. Folia Morphol (Warsz) 64:23–28. MacDonald ME, Hall BK. 2001. Altered timing of the extracellularmatrix-mediated epithelial-mesenchymal interaction that initiates mandibular skeletogenesis in three inbred strains of mice: development, heterochrony, and evolutionary change in morphology. J Exp Zool 291:258–273. Maddox BK, Garofalo S, Horton WA, Richardson MD, Trune DR. 1998. Craniofacial and otic capsule abnormalities in a transgenic mouse strain with a Col2a1 mutation. J Craniofac Genet Dev Biol 18:195–201. Merida-Velasco JA, Sanchez-Montesinos I, Espin-Ferra J, GarciaGarcia JD, Roldan-Schilling V. 1993. Developmental differences in the ossiﬁcation process of the human corpus and ramus mandibulae. Anat Rec 235:319–324. Merida-Velasco JR, Rodriguez-Vazquez JF, Merida-Velasco JA, Sanchez-Montesinos I, Espin-Ferra J, Jimenez-Collado J. 1999. Development of the human temporomandibular joint. Anat Rec 255:20–33. Mina M. 2001a. Morphogenesis of the medial region of the developing mandible is regulated by multiple signaling pathways. Cells Tissues Organs 169:295–301. Mina M. 2001b. Regulation of mandibular growth and morphogenesis. Crit Rev Oral Biol Med 12:276–300. Morimoto K, Hashimoto N, Suetsugu T. 1987. Prenatal developmental process of human temporomandibular joint. J Prosthet Dent 57:723–730. Nyska M, Nyska A, Swissa-Sivan A, Samueloff S. 1995. Histomorphometry of long bone growth plate in swimming rats. Int J Exp Pathol 76:241–245. Orliaguet T, Dechelotte P, Scheye T, Vanneuville G. 1993a. Relations between Meckel’s cartilage and the morphogenesis of the mandible in the human embryo. Surg Radiol Anat 15:41–46. Orliaguet T, Dechelotte P, Scheye T, Vanneuville G. 1993b. The relationship between Meckel’s cartilage and the development of the human fetal mandible. Surg Radiol Anat 15:113–118. Orliaguet T, Darcha C, Dechelotte P, Vanneuville G. 1994. Meckel’s cartilage in the human embryo and fetus. Anat Rec 238:491–497. Plessis JL, Caliot P, Midy D, Gomez H, Meunier JM. 1991. An atypical development of Meckel’s cartilage. Surg Radiol Anat 13:77–78. Pritchett JW. 1991. Growth plate activity in the upper extremity. Clin Orthop 268:235–242. Radlanski RJ, Lieck S, Bontschev NE. 1999. Development of the human temporomandibular joint: computer-aided 3D- reconstructions. Eur J Oral Sci 107:25–34. Radlanski RJ, Klarkowski MC. 2001. Bone remodeling of the human mandible during prenatal development. J Orofac Orthop 62:191–201. Radlanski RJ, Renz H, Klarkowski MC. 2003. Prenatal development of the human mandible: 3D reconstructions, morphometry and bone remodelling pattern, sizes 12–117 mm CRL. Anat Embryol (Berl) 207:221–232. Rodriguez-Vazquez JF, Merida-Velasco JR, Arraez-Aybar LA, Jimenez-Collado J. 1997a. A duplicated Meckel’s cartilage in a human fetus. Anat Embryol (Berl) 195:497–502. Rodriguez-Vazquez JF, Merida-Velasco JR, Merida-Velasco JA, Sanchez-Montesinos I, Espin-Ferra J, Jimenez-Collado J. 1997b. Development of Meckel’s cartilage in the symphyseal region in man. Anat Rec 249:249–254. Rosati R, Horan GS, Pinero GJ, Garofalo S, Keene DR, Horton WA, Vuorio E, de Crombrugghe B, Behringer RR. 1994. Normal long bone growth and development in type X collagen-null mice. Nat Genet 8:129–135. Shum L, Sakakura Y, Bringas P, Jr., Luo W, Snead ML, Mayo M, Crohin C, Millar S, Werb Z, Buckley S, et al. 1993. EGF abrogation-induced fusilli-form dysmorphogenesis of Meckel’s cartilage during embryonic mouse mandibular morphogenesis in vitro. Development 118:903–917. Tan DP, Nonaka K, Nuckolls GH, Liu YH, Maxson RE, Slavkin HC, Shum L. 2002. YY1 activates Msx2 gene independent of bone morphogenetic protein signaling. Nucl Acids Res 30:1213–1223. Tavakkoli-Jou M, Miller AJ, Kapila S. 1999. Mandibulofacial adaptations in a juvenile animal model of temporomandibular joint arthritis. J Dent Res 78:1426–1435. Trichilis A, Wroblewski J. 1997. Expression of p53 and hsp70 in relation to apoptosis during Meckel’s cartilage development in the mouse. Anat Embryol (Berl) 196:107–113. Tumer N, Gultan AS. 1999. Comparison of the effects of monoblock and twin-block appliances on the skeletal and dentoalveolar structures. Am J Orthod Dentofacial Orthop 116:460–468. Wang Y, Hu Y, Meng J, Li C. 2001. An ossiﬁed Meckel’s cartilage in two Cretaceous mammals and origin of the mammalian middle ear. Science 294:357–361. Yamasaki Y, Hayasaki H, Ogata T, Nakata M, Hamano Y. 1991. The stomatognathic function in a case of hemifacial hypertrophy: ﬁndings of mandibular movement. Shoni Shikagaku Zasshi 29: 186–195.