Chondroid Bone Research Articles

Synchronous chondroblastomas in the knee joint: A case report

IntroductionA chondroblastoma (CB) is a benign chondroid bone tumor that typically arises in growing children. It frequently occurs in the proximal tibia, femur, and humerus. However, the biological behavior of CBs remains unclear because of their rarity. Herein, we report a rare case of synchronous CBs arising on the bilateral sides of the knee joint, suggesting the etiology of chronological tumorigenesis.Presentation of caseAn 18-year-old Japanese man with a complaint of right knee pain was referred to our hospital. Radiography revealed an expanding osteolytic lesion in the right proximal tibia. A small lesion in the distal femur was detected on magnetic resonance imaging. A biopsy of the tibial lesion revealed a pathological diagnosis of CB. Two-stage curettages were performed in the tibia and femur, and the pathological diagnosis of the femoral lesion was CB. No recurrence had occurred for 5 years in the tibia and a year in the femur with stable ambulation and a full range of motion.DiscussionIn our case, the CBs in the proximal tibia and distal femur co-occurred, suggesting that the seed of the CB emerged before the separation of these two bones. The key point to the generation of CB is that its origin could be initiated during mesenchymal condensation before the separation and differentiation of bones as if continental drifts.ConclusionWe experienced a rare and suggestive case in CB etiology. An experience of synchronous CBs in the consecutive bones was suggestive of CB etiology and careful management.

Keratan sulfate as a marker for medullary bone in fossil vertebrates.

The ability to determine the sex of extinct dinosaurs by examining the bones they leave behind would revolutionize our understanding of their paleobiology; however, to date, definitive sex-specific skeletal traits remain elusive or controversial. Although living dinosaurs (i.e., extant birds) exhibit a sex-specific tissue called medullary bone that is unique to females, the confident identification of this tissue in non-avian archosaurs has proven a challenge. Tracing the evolution of medullary bone is complicated by existing variation of medullary bone tissues in living species; hypotheses that medullary bone structure or chemistry varied during its evolution; and a lack of studies aimed at distinguishing medullary bone from other types of endosteal tissues with which it shares microstructural and developmental characteristics, such as pathological tissues. A recent study attempted to capitalize on the molecular signature of medullary bone, which, in living birds, contains specific markers such as the sulfated glycosaminoglycan keratan sulfate, to support the proposed identification of medullary bone of a non-avian dinosaur specimen (Tyrannosaurus rex MOR 1125). Purported medullary bone samples of MOR 1125 reacted positively to histochemical analyses and the single pathological control tested (avian osteopetrosis) did not, suggesting the presence of keratan sulfate might serve to definitively discriminate these tissues for future studies. To further test these results, we sampled 20 avian bone pathologies of various etiologies (18 species), and several MB samples. Our new data universally support keratan sulfate as a reliable marker of medullary bone in birds. However, we also find that reactivity varies among pathological bone tissues, with reactivity in some pathologies indistinguishable from MB. In the current sample, some pathologies comprised of chondroid bone (often a major constituent of skeletal pathologies and developing fracture calluses in vertebrates) contain keratan sulfate. We note that beyond chemistry, chondroid bone shares many characteristics with medullary bone (fibrous matrix, numerous and large cell lacunae, potential endosteal origin, trabecular architecture) and medullary bone has even been considered by some to be a type of chondroid bone. Our results suggest that the presence of keratan sulfate is not exclusive evidence for MB, but rather must be used as one in a suite of criteria available for identifying medullary bone (and thus gravid females) in non-avian dinosaur specimens. Future studies should investigate whether there are definite chemical or microstructural differences between medullary bone and reactive chondroid bone that can discriminate these tissues.

Histomorphometric Analysis of Osseointegrated Grade V Titanium Mini Transitional Implants in Edentulous Mandible by Backscattered Scanning Electron Microscopy (BS-SEM)

The purpose of this study is to assess the use of grade V titanium mini transitional implants (MTIs) immediately loaded by a temporary overdenture. For this, a histomorphometric analysis of the bone area fraction occupancy (BAFO) was performed by backscattered scanning electron microscopy (BS-SEM). Four female patients were submitted to surgery in which two MTIs were installed and immediately loaded with a temporary acrylic prosthesis. During the same surgery, two regular diameter implants were placed inside the bone and maintained without mechanical load. After 8 months, the MTIs were extracted using a trephine and processed for ultrastructural bone analysis by BS-SEM, and the regular-diameter implants were loaded with an overdenture device. A total of 243 BAFOs of MTIs were analyzed, of which 94 were mainly filled with cortical bone, while 149 were mainly filled with trabecular bone. Bone tissue analysis considering the total BAFOs with calcified tissues showed 72.13% lamellar bone, 26.04% woven bone, and 1.82% chondroid bone without significant differences between the samples. This study revealed that grade V titanium used in immediately loaded MTI was successfully osseointegrated by a mature and vascularized bone tissue as assessed from the BAFO.

Extensive chondroid bone in juvenile duck limbs hints at accelerated growth mechanism in avian skeletogenesis.

Modern altricial birds are the fastest growing vertebrates, whereas various degrees of precocity (functional maturity) result in slower growth. Diaphyseal osteohistology, the best proxy for inferring relative growth rates in fossils, suggests that in the earliest birds, posthatching growth rates were more variable than in modern representatives, with some showing considerably slow growth that was attributed to their assumed precocial flight abilities. For finding clues how precocial or altricial skeletogenesis and related growth acceleration could be traced in avian evolution, as a case study we investigated the growing limb diaphyseal histology in an ontogenetic series of ducks which, among several other avian taxa, show a combination of altricial wing and precocial leg development. Here we report the unexpected discovery that chondroid bone, a skeletal tissue family intermediate between cartilage and bone, extensively contributes to the development of limb bone shaft in ducks up to at least 30 days posthatching age. To our knowledge, chondroid bone has never been reported in such quantities and with an ontogenetically extended deposition period in post‐embryonic, non‐pathological periosteal bone formation of any tetrapod limb. It shows transitional cellular/lacunar morphologies and matrix staining properties between cartilage and woven bone and takes a significant part in the diametric growth of the limb bone shaft. Its amount and distribution through duckling ontogeny seems to be associated with the disparate functional and growth trajectories of the altricial wings vs. precocial legs characteristic of duck limb development. The presence of isogenous cell groups in the periosteal chondroid bone implies that cartilage‐like interstitial growth took place before matrix mineralization complementing appositional bone growth. Based on these characteristics and on its fast formation rate in all previously reported normal as well as pathological cases, we suggest that chondroid bone in ducks significantly accelerates diametric limb bone growth. Related to this growth acceleration, we hypothesize that chondroid bone may be generally present in the growing limb bones of modern birds and hence may have key skeletogenic importance in achieving extreme avian growth rates and placing birds among the fastest growing vertebrates. Thus, we encourage future studies to test this hypothesis by investigating the occurrence of chondroid bone in a variety of precocial and altricial bird species, and to explore the presence of similar tissues in the growing limbs of other extant and extinct tetrapods in order to understand the evolutionary significance of chondroid bone in accelerated appendicular skeletogenesis.

Cranial joint histology in the mallard duck (Anas platyrhynchos): new insights on avian cranial kinesis.

The evolution of avian cranial kinesis is a phenomenon in part responsible for the remarkable diversity of avian feeding adaptations observable today. Although osteological, developmental and behavioral features of the feeding system are frequently studied, comparatively little is known about cranial joint skeletal tissue composition and morphology from a microscopic perspective. These data are key to understanding the developmental, biomechanical and evolutionary underpinnings of kinesis. Therefore, here we investigated joint microstructure in juvenile and adult mallard ducks (Anas platyrhynchos; Anseriformes). Ducks belong to a diverse clade of galloanseriform birds, have derived adaptations for herbivory and kinesis, and are model organisms in developmental biology. Thus, new insights into their cranial functional morphology will refine our understanding of avian cranial evolution. A total of five specimens (two ducklings and three adults) were histologically sampled, and two additional specimens (a duckling and an adult) were subjected to micro-computed tomographic scanning. Five intracranial joints were sampled: the jaw joint (quadrate-articular); otic joint (quadrate-squamosal); palatobasal joint (parasphenoid-pterygoid); the mandibular symphysis (dentary-dentary); and the craniofacial hinge (a complex flexion zone involving four different pairs of skeletal elements). In both the ducklings and adults, the jaw, otic and palatobasal joints are all synovial, with a synovial cavity and articular cartilage on each surface (i.e. bichondral joints) ensheathed in a fibrous capsule. The craniofacial hinge begins as an ensemble of patent sutures in the duckling, but in the adult it becomes more complex: laterally it is synovial; whereas medially, it is synostosed by a bridge of chondroid bone. We hypothesize that it is chondroid bone that provides some of the flexible properties of this joint. The heavily innervated mandibular symphysis is already fused in the ducklings and remains as such in the adult. The results of this study will serve as reference for documenting avian cranial kinesis from a microanatomical perspective. The formation of: (i) secondary articular cartilage on the membrane bones of extant birds; and (ii) their unique ability to form movable synovial joints within two or more membrane bones (i.e. within their dermatocranium) might have played a role in the origin and evolution of modern avian cranial kinesis during dinosaur evolution.

Evolutionary origin of endochondral ossification: the transdifferentiation hypothesis.

The vertebrate endoskeleton results from the piecemeal assembly of bone and cartilage as well as additional types of calcified extracellular matrices produced by seemingly hybrid cell types of intermediate phenotypes between osteoblasts and chondrocytes. Hence, shedding light on the emergence and subsequent diversification of skeletal tissues represents a major challenge in vertebrate evolutionary developmental biology. A 150-year-old debate in the field was recently solved by lineage tracing experiments demonstrating that, during mouse endochondral bone development, a subset of chondrocytes evades apoptosis and transdifferentiates into osteoblasts at the chondro-osseous junction. Here, we interpret these new data from a broad phylogenetic perspective, integrating fossil, histological, cellular, and genetic evidence from a wide range of vertebrates. We propose a testable scenario according to which transdifferentiation played a fundamental role in the emergence of endochondral ossification, an osteichthyan-specific evolutionary novelty. The remarkable skeletal cell plasticity might be contingent on the similar architectures of the osteoblastic and chondrocytic gene regulatory networks, thereby providing a unifying mechanism underlying both complete transdifferentiation as well as partial cell type conversions observed in intermediate skeletal tissues such as the chondroid bone or globuli ossei.

An immunohistochemical study of matrix proteins in the craniofacial cartilage in midterm human fetuses

Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes.

Growth of the mandible and biological characteristics of the mandibular condylar cartilage

Mandibular condylar cartilage is the center of greatest growth in the craniofacial complex, and is associated with maxillofacial skeleton morphogenesis and temporomandibular joint function. The condylar process grows in a wide range of directions from anterosuperior to posterior, resulting in highly diverse mandibular growth and morphology. Condylar growth direction is closely related to mandibular displacement direction and vertical jaw deviations (i.e., high or low angle). Condylar cartilage, which is ontogenetically designated secondary cartilage, differs from other primary cartilage (e.g., articular cartilage and growth plate of a long bone cranial base cartilage, nasal septal cartilage) in the following ways. (1) Condylar cartilage is a heterogeneous tissue containing fibroblasts, osteochondral progenitor cells, and chondrocytes. (2) Type I collagen, which is derived from progenitor cells, and cartilage-characteristic type II collagen are colocalized in the cartilaginous cell layer. Colocalization of both collagen types may be an adaptation to the complex biomechanical environments of condylar cartilage. (3) Peripheral condylar cartilage contains chondroid bone, a specialized calcified tissue with morphological properties intermediate between those of bone and cartilage. This hybrid tissue may play an important role in regulating different rates of bone formation in intramembranous and endochondral ossification, allowing for highly diverse growth directions and condylar and maxillofacial morphology.

Comparative analysis of a teleost skeleton transcriptome provides insight into its regulation

An articulated endoskeleton that is calcified is a unifying innovation of the vertebrates, however the molecular basis of the structural divergence between terrestrial and aquatic vertebrates, such as teleost fish, has not been determined. In the present study long-read next generation sequencing (NGS, Roche 454 platform) was used to characterize acellular perichondral bone (vertebrae) and chondroid bone (gill arch) in the gilthead sea bream (Sparus auratus). A total of 15.97 and 14.53Mb were produced, respectively from vertebrae and gill arch cDNA libraries and yielded 32,374 and 28,371 contigs (consensus sequences) respectively. 10,455 contigs from vertebrae and 10,625 contigs from gill arches were annotated with gene ontology terms. Comparative analysis of the global transcriptome revealed 4249 unique transcripts in vertebrae, 4201 unique transcripts in the gill arches and 3700 common transcripts. Several core gene networks were conserved between the gilthead sea bream and mammalian skeleton. Transcripts for putative endocrine factors were identified in acellular gilthead sea bream bone suggesting that in common with mammalian bone it can act as an endocrine tissue. The acellular bone of the vertebra, in contrast to current opinion based on histological analysis, was responsive to a short fast and significant (p<0.05) down-regulation of several transcripts identified by NGS, osteonectin, osteocalcin, cathepsin K and IGFI occurred. In gill arches fasting caused a significant (p<0.05) down-regulation of osteocalcin and up-regulation of MMP9.

骨, 軟骨と軟骨様骨の形態的相違:光学顕微鏡的および電子顕微鏡的研究

骨, 軟骨と軟骨様骨の形態的相違:光学顕微鏡的および電子顕微鏡的研究

Chondroblastoma of the femoral neck as a cause of hip synovitis

Chondroblastoma is a rare benign chondroid bone tumor, which typically arises from the epiphysis of a long tubular bone. We present a 13-year-old girl with persistent hip synovitis caused by a chondroblastoma that arose from the femoral neck (metaphysis) and uniquely extended extraosseously into the hip joint. Computed tomography scan clearly demonstrated a tumoral lesion of the left femoral neck and a periosteal reaction along the anterior cortex of the femur, distal to the legion. Magnetic resonance imaging showed reactive synovitis with marked joint effusion of the hip and an extensive edema in the proximal femur and the surrounding soft tissues. Aneurysmal bone cysts formation secondary to chondroblastoma was confirmed by histologic examinations of the excised specimens. Complete relief of pain and an improvement in the range of movement of the hip joint was obtained after surgical resection of the tumor.

Cellular morphology and markers of cartilage and bone in the marine teleost Sparus auratus

Modifications have been characterised in terms of cellular organisation and the extracellular matrix (ECM) during bone ontogeny in the sea bream (Sparus auratus). During endochondral development, the agglomeration of matrix-secreting cells gives rise to chondrones; these chondrones frequently contain proliferating-cell-nuclear-antigen-positive cells, which subsequently become large collagen-II-positive cells with the characteristics of chondrocytes. Moreover, the matrix:cell ratio within the perichondrium increases, accompanied by a modification in ECM composition. Mineralisation of cartilage ECM is marked by a rapid fall in cell number, the switching off of collagen II transcription and the switching on of collagen X transcription, followed by collagen I transcription and bone mineralisation. The formation of dermal structures initiated upon the condensation of mesenchyme cells defines the future location of the dermal bone. Subsequent cellular differentiation gives rise to cells on the bone surface; these cells are positive for collagen I and osteonectin transcripts. The fish skeleton, with the exception of vertebrae, tends to comprise flattened bones that are covered by a monolayer of cells, the periosteum. A third type of tissue, present in gills, consists of chondrocyte-like cells embedded in a mineralised matrix resembling chondroid bone in mammals. The results suggest that the cellular organisation and ontogeny of endochondral and dermal bone in the sea bream are similar to those described in other vertebrates.

CD44: survival and metastasis in chondrosarcoma

Recent studies have shown abnormal expression of CD44s and some of its isoforms in many human malignancies, but little is known about the presence of CD44 in chondrosarcoma. In this study the expression of CD44s and two variant isoforms was evaluated. It was assumed that abnormalities in these receptor proteins may be associated with clinical outcome of the patients. Thirty paraffin-embedded chondrosarcoma samples were immunostained with monoclonal antibodies for CD44s, CD44v5 and CD44v6. Two independent examiners who were unaware of the clinical status of the patients evaluated the immunohistochemical results. The percentage of CD44-positive cells was scored semiquantitatively. A rate of higher than 10% was considered as overexpression. Among the 30 patients (median age 50 years) there were 22 conventional chondrosarcomas, two dedifferentiated chondrosarcomas, two extraskeletal chondrosarcomas, and one periostal, mesenchymal, clear cell and myxoid chondrosarcoma each. In the immunochemistry staining overexpression (>10% of cells) of CD44s was shown in 56.7% (17 of 30), of CD44v5 in 43.3% (13 of 30) and of CD44v6 in 6.7% (two of 30) of the tumors. Four grade III chondrosarcomas (80%) and 10 (71.4%) grade II chondrosarcomas showed overexpression for CD44s, whereas CD44s was overexpressed in only three (27.3%) grade I chondrosarcomas. Cox regression suggests overexpression of CD44s to be an additional prognostic marker for chondroid bone tumors independent of grading and other covariates. Overexpression of CD44s correlated significantly with metastatic potential and with poorer survival in patients with chondrosarcoma. CD44s might be an independent additional marker, but small sample size remains to be considered.

Repair process after fibrocartilaginous enthesis drilling: histological study in a rabbit model

Background.Disorders of the enthesis are often a consequence of sports injuries. However, there is uncertainty regarding the process of mechanical stress-related injuries at the enthesis and the subsequent repair process of the injured tissues. To elucidate the repair process of the fibrocartilaginous enthesis, we studied the repair of injured fibrocartilaginous enthesis and the morphological characteristics of the repaired tissue. Methods.We drilled 0.5-mm holes in the right tibial insertion of the patellar tendon of Japanese white rabbits, with their own left sides serving as controls. Specimens harvested at 1, 2, 4, 6, 8, and 12 weeks were examined histologically. Morphologically, the ratios of calcified fibrocartilage–bone interface lengths to enthesial lengths were compared between the control and surgical groups. Results.Repair initiation was observed in the deep bone layer at 1 week, with remarkable progress at 2 weeks. Repair at the enthesis and neoosteogenesis in deep bone layers were detected at 4 weeks, and the drill hole disappeared at 6 weeks. The tendon was partially invaded by fibrocartilage-covered chondroid bone at 8 weeks, and regenerated fibrocartilaginous enthesis and increased calcified fibrocartilage–bone interface irregularity was identified at 12 weeks. The ratios of calcified fibrocartilage–bone interface lengths to enthesial lengths were significantly greater in the surgical group than in the control group. Conclusions.Repair progressed from bone to fibrocartilage and ended at fibrous tissue. cancellous bone disruption triggered repair in all layers. Removal of the subchondral plate enabled infiltration of nutrients via blood vessels, with the underlying bone acting as a scaffold for the regenerating fibrocartilage.

Development of the dermal skeleton in Alligator mississippiensis (Archosauria, Crocodylia) with comments on the homology of osteoderms

The dermal skeleton (=exoskeleton) has long been recognized as a major determinant of vertebrate morphology. Until recently however, details of tissue development and diversity, particularly among amniotes, have been lacking. This investigation explores the development of the dermatocranium, gastralia, and osteoderms in the American alligator, Alligator mississippiensis. With the exception of osteoderms, elements of the dermal skeleton develop early during skeletogenesis, with most initiating ossification prior to mineralization of the endoskeleton. Characteristically, circumoral elements of the dermatocranium, including the pterygoid and dentigerous elements, are among the first to form. Unlike other axially arranged bones, gastralia develop in a caudolateral to craniomedial sequence. Osteoderms demonstrate a delayed onset of development compared with the rest of the skeleton, not appearing until well after hatching. Osteoderm development is asynchronous across the body, first forming dorsally adjacent to the cervical vertebrae; the majority of successive elements appear in caudal and lateral positions. Exclusive of osteoderms, the dermal skeleton initiates osteogenesis via intramembranous ossification. Following the establishment of skeletal condensations, some preossified spicules become engorged with many closely packed clusters of chondrocyte-like cells in a bone-like matrix. This combination of features is characteristic of chondroid bone, a tissue otherwise unreported among nonavian reptiles. No secondary cartilage was identified in any of the specimens examined. With continued growth, dermal bone (including chondroid bone) and osteoid are resorbed by multinucleated osteoclasts. However, there is no evidence that these cells contribute to the rugose pattern of bony ornamentation characteristic of the crocodylian dermatocranium. Instead, ornamentation develops as a result of localized concentrations of bone deposited by osteoblasts. Osteoderms develop in the absence of osteoblastic cells, osteoid, and periosteum; bone develops via the direct transformation of the preexisting dense irregular connective tissue. This mode of bone formation is identified as metaplasia. Importantly, it is also demonstrated that osteoderms are not histologically uniform but involve a range of tissues including calcified and uncalcified dense irregular connective tissue. Between taxa, not all osteoderms develop by homologous processes. However, it is concluded that all osteoderms may share a deep homology, connected by the structural and skeletogenic properties of the dermis.

Multifocal mesenchymal hamartoma of the chest wall

Chest wall hamartomas are extremely rare. Frequently mesenchymal hamartomas are presented as a single mass and contain some primitive mesenchymal elements such as chondroid and trabecular bone structures. A 60-year-old man presented to hospital with chest pain. Thirteen years earlier, his CXR and thoracic CT showed three masses on the right and two masses on the left, but he had not received any treatment thereafter. His CT showed the same masses present 13 years earlier, but they were bigger and right thoracotomy was undertaken. At thoracotomy, two sections of the mass in the right posterior mediastinum and one section of the mass in the right apex were excised. They had an occasional bloody appearance and contained small cystic areas, and some areas were extremely hard. Microscopic examination showed that the lesions consisted of mature adipose tissue, a large number of veins of different diameters and collagen tissue. Besides, primitive mesenchymal elements, lymphoid cell accumulations and trabecular bone structures were seen focally. Bilateral chest wall hamartomas are extremely rare and may be confused with malignancy.

Chondroid bone and secondary cartilage contribute to apical dentary growth in juvenile Atlantic salmon

The microstructure and tissue composition of the dentary bone in Atlantic salmon salmo salar parr were examined using a variety of histological and whole‐mount techniques. Proximally, the dentary is composed of typical cellular lamellar bone with Sharpey's fibres extending dorsally, proximally and ventrally. Meckel's cartilage is located medially through the entire length of the dentary, and degrades distally resulting in a short transitional zone between hyaline cartilage and connective tissue. At the distal tip of the dentary, isogenic clusters of chondrocytes of periosteal origin were observed secreting small amounts of pericellular cartilage matrix within the bone matrix. These characteristics are highly indicative of secondary chondrogenesis, and suggest that the apical part of the dentary bone in Atlantic salmon does not grow via‘pure’ intramembranous ossification, but rather via a modified mode of periosteal ossification involving secondary cartilage and chondroid bone. Furthermore, the unusual mode of gender‐related dentary growth (kype formation) in adult male Atlantic salmon could be the continuation of a general mode of salmonid apical dentary growth.

Transdifferentiation of dense connective tissue to chondroid bone in lordotic vertebrae of sea bass ( Dicentrarchus labrax L.)

Cartilage is known to be present in many invertebrates. I discuss the types of cartilage found in extant invertebrates and how such cartilages inform our understanding of the evolutionary origin of vertebrate cartilages and of the vertebrate notochord. Discussion of chondroid, mineralisation of cartilage, the formation of cartilage by notochordal cells and the evolutionary origins of cartilage complete the chapter.

A new transplant bone for maxillary alveolar cleft

An innovative technique with distraction osteogenesis has been developed in our research group to explore autogenous bone transplantation into craniofacial bone defects. This technique was designed to investigate bone-marrow transplantion using a chondroid or fibula bone graft into simulated alveolar bone defects in mice in terms of the osteogenic process and activity. As an experimental model of maxillary alveolar bone cleft available for testing bone-inductive materials, a critical-size defect was formed in the pre-maxillary bone of male mice using a surgical trephine bur with a low-speed dental engine. Distraction osteogenesis was performed using an external fixation device. The osteotomy site was occupied by an external callus consisting of hyaline cartilage with a large quantity of chondroid bone. Moreover, bone remodelling with new bone formation was demonstrated 30 days after the transplantation. Bone adhesion was better in chondroid bone grafting than in fibula bone grafting. The present findings are the first to demonstrate the potential of chondroid bone transplantation as a new therapeutic system of bone grafting, suitable for bone substitutes in craniofacial bone defects.

Mandibular coronoid process in parathyroid hormone-related protein-deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling.

Parathyroid hormone-related protein (PTHrP) null mutant mice were analyzed to investigate an additional role for PTHrP in cell differentiation. We found ectopic cartilage formation in the mandibular coronoid process in newborn mice. While many previous studies involving PTHrP gene knockout mouse have shown that the cartilage in various regions becomes smaller, this is the first report showing an "increase" of cartilage volume. Investigations of mandibular growth using normal mice indicated that coronoid secondary cartilage never formed from E 15 to d 4, but small amount of cartilage temporally formed at d 7, and this also applies to PTHrP-wild type mice. Therefore, PTHrP deficiency consequently advanced the secondary cartilage formation, which is a novel role of PTHrP in chondrocyte differentiation. In situ hybridization of matrix proteins showed that this coronoid cartilage had characteristics of the lower hypertrophic cell zone usually present at the site of endochondral bone formation and/or "chondroid bone" occasionally found in distraction osteogenesis. In addition, the coronoid process in the PTHrP-deficient mouse also showed abnormal expansion of bone marrow and an increase in the number of multinucleated osteoclasts, an indication of abnormal bone modeling. These results indicate that PTHrP is involved in bone modeling as well as in chondrocyte differentiation. In situ hybridization of matrix protein mRNAs in the abnormal mandibular condylar cartilage revealed that this cartilage was proportionally smaller, supporting previous immunohistochemical results.