Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts.

Chondrocytes proliferate and mature into hypertrophic chondrocytes. Vascular invasion into the cartilage occurs in the terminal hypertrophic chondrocyte layer, and terminal hypertrophic chondrocytes die by apoptosis or transdifferentiate into osteoblasts. Runx2 is essential for osteoblast differentiation and chondrocyte maturation. Runx2-deficient mice are composed of cartilaginous skeletons and lack the vascular invasion into the cartilage. However, the requirement of Runx2 in the vascular invasion into the cartilage, mechanism of chondrocyte transdifferentiation to osteoblasts, and its significance in bone development remain to be elucidated. To investigate these points, we generated Runx2fl/flCre mice, in which Runx2 was deleted in hypertrophic chondrocytes using Col10a1 Cre. Vascular invasion into the cartilage was similarly observed in Runx2fl/fl and Runx2fl/flCre mice. Vegfa expression was reduced in the terminal hypertrophic chondrocytes in Runx2fl/flCre mice, but Vegfa was strongly expressed in osteoblasts in the bone collar, suggesting that Vegfa expression in bone collar osteoblasts is sufficient for vascular invasion into the cartilage. The apoptosis of terminal hypertrophic chondrocytes was increased and their transdifferentiation was interrupted in Runx2fl/flCre mice, leading to lack of primary spongiosa and osteoblasts in the region at E16.5. The osteoblasts appeared in this region at E17.5 in the absence of transdifferentiation, and the number of osteoblasts and the formation of primary spongiosa, but not secondary spongiosa, reached to levels similar those in Runx2fl/fl mice at birth. The bone structure and volume and all bone histomophometric parameters were similar between Runx2fl/fl and Runx2fl/flCre mice after 6 weeks of age. These findings indicate that Runx2 expression in terminal hypertrophic chondrocytes is not required for vascular invasion into the cartilage, but is for their survival and transdifferentiation into osteoblasts, and that the transdifferentiation is necessary for trabecular bone formation in embryonic and neonatal stages, but not for acquiring normal bone structure and volume in young and adult mice.

CONSEQUENCES OF MICROSEQUENCES OF MICROCIRCULATORY DISTRURBANCES OF ORAL MUCOSA IN MODELING OF RHEUMATOID ARTHRITIS.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia and the destruction of cartilage and bone with unclear morphogenesis of pathological changes in oral cavity. Simultaneously microcirculatory disturbance is important link of pathogenesis in many pathological conditions in oral cavity with inflammatory consequences. The aim of this study was to determine importance of microcirculatory disturbance of oral mucosa in modeling of rheumatoid arthritis. Experimental investigation has been performed with modeling RA on laboratory white male mice according to described before method. Investigated groups were formed according to severity manifestation as ankle changes using digital calipers measuring. The specimens of soft tissues of the oral cavity were stained with hematoxylin and eosin, according to van Gieson, according to Rego after the routine proceeding. Morphometric studies were performed with estimation of volumes of specific vascular density in microcirculatory bed, density of connective tissue in lamina propria and area of tissue with ischemia. It was detected that disturbance of oral mucosae microvasculature is formed in rheumatoid arthritis with strong correlation relationship between specific densities of microcirculatory bed vessels and rheumatoid arthritis severity (r=0.74). Development of ischemic area indicates strong correlation relationship between ischemic area and rheumatoid arthritis severity also (r=0.72) and it could be connected with changes in microvasculature (r=0.82). Development of sclerotic changes in the lamina propria of the mucosa could is characterized by increased area of connective tissue from 21.37±2.82% to 34.97±2.26 %.

The Size of Intramedullary Fixation Affects Endochondral-Mediated Angiogenesis During Fracture Repair.

OBJECTIVES: To explore the effect of intramedullary pin size on the biology of a healing fracture, specifically endochondral angiogenesis. We hypothesized that fracture fixation with a smaller pin would permit greater interfragmentary strain resulting in increased total amount of vascular endothelial growth factor within the callus and greater angiogenesis compared to fixation with a larger pin. METHODS: Transverse mid-shaft femur fractures in 8-week-old mice were fixed with either a 23-gauge (G) or 30-G pin. Differences in interfragmentary strain at the fracture site were estimated between cohorts. A combination of histology, gene expression, serial radiography, and microcomputed tomography with and without vascular contrast agent were used to assess fracture healing and vascularity for each cohort. RESULTS: Larger soft-tissue callus formation increased vascular endothelial growth factor-A expression, and a corresponding increase in vascular volume was observed in the higher strain, 30-G cohort. Radiographic analysis demonstrated earlier hard callus formation with greater initial interfragmentary strain, similar rates of union between pin size cohorts, yet delayed callus remodeling in mice with the larger pin size. CONCLUSIONS: These findings suggest that the stability conferred by an intramedullary nail influences endochondral angiogenesis at the fracture.

Pannus inflammation in sacroiliitis following immune pathological injury and radiological structural damage: a study of 193 patients with spondyloarthritis.

BACKGROUND: The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS: Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. RESULTS: In early sacroiliitis (grade 0-1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1-13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. CONCLUSIONS: Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up.

Nonvascularized Cartilage Grafts Versus Vascularized Cartilage Flaps: Comparison of Cartilage Quality 6 Months After Transfer.

PURPOSE: Subchondral perfusion of osteochondral grafts has been shown to be important in preventing long-term cartilage degeneration. In carpal reconstruction, subchondral perfusion from the graft bed is limited. This study's purpose was to compare the histological characteristics of cartilage in osteochondral grafts supported by synovial imbibition alone to cartilage of vascularized osteochondral flaps that have both synovial and vascular pedicle perfusion. METHODS: Two adjacent osteochondral segments were harvested on the medial femoral trochlea in domestic 6- to 8-month-old pigs. Each segment measured approximately 12 mm × 15 mm × 17 mm. One segment was maintained on the descending geniculate artery vascular pedicle. The adjacent segment was separated from the pedicle to serve as a nonvascularized graft. A thin layer of methylmethacrylate cement was used to line the harvest site defect to prevent vascular ingrowth to the subsequently replaced specimens. The pigs were maintained on a high-calorie feed and returned to ambulation and full weight-bearing on the surgical legs. The animals were sacrificed after 6 months and the specimens were reharvested, sectioned, and examined. The cartilage was graded by 2 pathologists blinded to the origin of specimens as vascularized flaps or nonvascularized grafts. RESULTS: All specimens were assigned scores utilizing the International Cartilage Repair Society grading system. Scoring for chondrocyte viability, cartilage surface morphology, and cell and matrix appearance was significantly higher in the vascularized osteochondral group than in the graft group. CONCLUSIONS: When deprived of subchondral perfusion from underlying bone, osteochondral vascularized flaps in an intrasynovial environment demonstrate superior cartilage quality and survival compared with nonvascularized grafts. CLINICAL RELEVANCE: In locations in which perfusion from surrounding bone may be limited (ie, proximal scaphoid or proximal lunate reconstruction), articular reconstruction using vascularized osteochondral flaps will yield superior cartilage organization and architecture than nonvascularized osteochondral grafts. The clinical and functional relevance of this finding requires further study.

VEGF promotes cartilage angiogenesis by phospho-ERK1/2 activation of Dll4 signaling in temporomandibular joint osteoarthritis caused by chronic sleep disturbance in Wistar rats.

Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD. Furthermore, we show that VEGF-induce activation of ERK1/2, which in turn, increases Dll4 expression. Together, our results suggest that CSD can cause OA-like pathological alterations in the rat TMJ by increasing angiogenesis.

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification.

UNLABELLED: : Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also known as bone marrow-derived mesenchymal stromal/stem cells), adipose-derived stromal cells (ASC) have so far failed to form a bone organ by ECO. The goal of the present study was to assess whether priming human ASC to a defined stage of chondrogenesis in vitro allows their autonomous ECO upon ectopic implantation. ASC were cultured either as micromass pellets or into collagen sponges in chondrogenic medium containing transforming growth factor-ß3 and bone morphogenetic protein-6 for 4 weeks (early hypertrophic templates) or for two additional weeks in medium supplemented with ß-glycerophosphate, l-thyroxin, and interleukin1-ß to induce hypertrophic maturation (late hypertrophic templates). Constructs were implanted in vivo and analyzed after 8 weeks. In vitro, ASC deposited cartilaginous matrix positive for glycosaminoglycans, type II collagen, and Indian hedgehog. Hypertrophic maturation induced upregulation of type X collagen, bone sialoprotein, and matrix metalloproteinase13 (MMP13). In vivo, both early and late hypertrophic templates underwent cartilage remodeling, as assessed by MMP13- and tartrate-resistant acid phosphatase-positive staining, and developed bone ossicles, including bone marrow elements, although to variable degrees of efficiency. In situ hybridization for human-specific sequences and staining with a human specific anti-CD146 antibody demonstrated the direct contribution of ASC to bone and stromal tissue formation. In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro. SIGNIFICANCE: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice.

Anatomy of the Vascularized Lateral Femoral Condyle Flap.

BACKGROUND: The perforators of the free lateral femoral condyle flap have yet to be adequately described in humans. Therefore, the authors investigated the perforator vessels of the lateral femoral condyle flap in an anatomical study and discussed potential clinical applications with a particular interest in its indication with vascularized bone and/or iliotibial band for tendon repair surgery. METHODS: The authors dissected thighs of 28 cadavers to evaluate the anatomical properties of perforator vessels that branch from the superior lateral genicular artery and supply bone, cartilage, subcutaneous tissue, and the iliotibial band of the lateral femoral condyle. RESULTS: In each dissected thigh, the superior lateral genicular artery was present and the average pedicle length was 38 ± 10 mm. The average diameter of the superior lateral genicular artery, proximal to its distribution into the deep articular and superficial patellar branches, was 2 ± 0.5 mm. A communication between deep articular and superficial patellar branches was seen in 96 percent of the dissected thighs. In 24 cases (86 percent), the authors were able to show the iliotibial band perforating vessel and harvest a free lateral femoral condyle flap as an osteochondral fasciocutaneous bone flap with vascularized tendon. CONCLUSIONS: Altogether, the authors' results indicate that the blood supply of the lateral femoral condyle flap is consistent and the lateral femoral condyle flap could serve as a free composite flap for complex indications in hand or limb reconstructive surgery. Clinical studies to compare the lateral femoral condyle to other well-established microsurgical free flaps are warranted.

Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis-susceptible sites in foals revealed by SWI 3T MRI.

Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non-invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility-weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) day-old foals, with minimal joint loading after birth, was performed. SWI and 3D images revealed the EGC vascular architecture without a contrast agent, and matched histologic observations. No vascular lesions were identified. There was no difference in the vascular density and architecture between control and OC specimens, but a striking difference in vascular pattern was seen at the OC-predilected site in the lateral ridge of the trochlea in all specimens, when compared to the medial ridge of the trochlea, where OC lesions are rarely observed. This site was less ossified with more perichondrial vessels not yet bridging with the subchondral bone. Furthermore, the mean vascular density of all specimens was significantly higher at this site. We speculate that joint morphology and focal internal trauma on this site with a unique vascular architecture may trigger ischemic events at this site. SWI permitted visualization of EGC in young foals with a clinical 3T MRI and paves the way for non-destructive longitudinal studies to improve understanding of OC in all species. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1539-1546, 2016.

Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus.

Endochondral ossification is a developmental process by which cartilage is replaced by bone. Terminally differentiated hypertrophic chondrocytes are calcified, vascularized, and removed by chondroclasts before bone matrix is laid down by osteoblasts. In mammals, the malleus is one of three auditory ossicles that transmit vibrations of the tympanic membrane to the inner ear. The malleus is formed from a cartilaginous precursor without growth plate involvement, but little is known about how bones of this type undergo endochondral ossification. Here, we demonstrate that in the processus brevis of the malleus, clusters of osteoblasts surrounding the capillary loop produce bone matrix, causing the volume of the capillary lumen to decrease rapidly in post-weaning mice. Synchrotron X-ray tomographic microscopy revealed a concentric, cylindrical arrangement of osteocyte lacunae along capillaries, indicative of pericapillary bone formation. Moreover, we report that overexpression of Fosl1, which encodes a component of the AP-1 transcription factor complex, in osteoblasts significantly blocked malleal capillary narrowing. These data suggest that osteoblast/endothelial cell interactions control growth plate-free endochondral ossification through 'osteogenic capillaries' in a Fosl1-regulated manner.

Normal sonoanatomy of the paediatric entheses including echostructure and vascularisation changes during growth.

OBJECTIVES: To describe the sonoanatomy of paediatric lower-limb entheses according to age and gender. We studied sites that most commonly involved entheses in spondyloarthritis. METHODS: We studied 41 consecutive healthy children (20 girls, 21 boys; age 2-15 years) divided into four age groups: 2-4 years (n = 9), 5-7 years (n = 11), 8-12 years (n = 12) and 13-15 years (n = 9). Ultrasound was used to obtain both transverse and longitudinal views of each enthesis. We assessed the echostructural components of the lower limb entheses and the vascularisation of the entheses and cartilage according to the different anatomical sites and age and gender. RESULTS: At all sites on B-mode, cartilage and tendon thicknesses showed positive or negative correlations with age (P < 0.0001). Side-to-side correlations were good (P < 0.0001 overall) and stronger for cartilage (r, 0.77-0.97) than for tendon thickness (r, 0.58-0.63). Agreement between the two sides for discrete data was very good to excellent (kappa, 0.77-1). Cartilage thickness at the various sites was significantly greater in boys than in girls (P ≤ 0.05). Tendon thickness was not significantly influenced by gender. Blood vessels were seen within the cartilage with differences across age groups. CONCLUSIONS: This study provides the first data on normal entheseal sonoanatomy and vascularisation in children. KEY POINTS: • The tendons of children exhibit the same fibrillar structure as adults • Tendon thickness at enthesis insertion in children is not influenced by gender • Cartilage thickness in children decreases with advancing age and varies with gender.

Vascularization of engineered cartilage constructs in a mouse model.

Tissue engineering of cartilage tissue offers a promising method for reconstructing ear, nose, larynx and trachea defects. However, a lack of sufficient nutrient supply to cartilage constructs limits this procedure. Only a few animal models exist to vascularize the seeded scaffolds. In this study, polycaprolactone (PCL)-based polyurethane scaffolds are seeded with 1 × 10(6) human cartilage cells and implanted in the right hind leg of a nude mouse using an arteriovenous flow-through vessel loop for angiogenesis for the first 3 weeks. Equally seeded scaffolds but without access to a vessel loop served as controls. After 3 weeks, a transposition of the vascularized scaffolds into the groin of the nude mouse was performed. Constructs (verum and controls) were explanted 1 and 6 weeks after transposition. Constructs with implanted vessels were well vascularized. The amount of cells increased in vascularized constructs compared to the controls but at the same time noticeably less extracellular matrix was produced. This mouse model provides critical answers to important questions concerning the vascularization of engineered tissue, which offers a viable option for repairing defects, especially when the desired amount of autologous cartilage or other tissues is not available and the nutritive situation at the implantation site is poor.

Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage.

Growth plate injuries often result in undesirable bony repair causing bone growth defects, for which the underlying mechanisms are unclear. Whilst the key importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well-known in bone development and fracture repair, its role during growth plate bony repair remains unexplored. Using a rat tibial growth plate injury repair model with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5 mg/kg) after injury, this study examined the roles of VEGF-driven angiogenesis during growth plate bony repair. Histology analyses observed isolectin-B4-positive endothelial cells and blood vessel-like structures within the injury site on days 6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like structures within the injury site (P<0.05). Compared with untreated controls, anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal repair tissue, but decreased bony tissue at the injury site at day 14 (P<0.01). Consistently, microcomputed tomography analysis of the injury site showed significantly decreased bony repair tissue after treatment (P<0.01). RT-PCR analyses revealed a significant decrease in osteocalcin (P<0.01) and a decreasing trend in Runx2 expression at the injury site following treatment. Furthermore, growth plate injury-induced reduced tibial lengthening was more pronounced in anti-VEGF-treated injured rats on day 60, consistent with the observation of a significantly increased height of the hypertrophic zone adjacent to the growth plate injury site (P<0.05). These results indicate that VEGF is important for angiogenesis and formation of bony repair tissue at the growth plate injury site as well as for endochondral bone lengthening function of the uninjured growth plate.

[Investigation of simple and complex prelamination of vascularized flaps in experiment].

Prelamination, permitting improvement not esthetics only, but also function of the damaged region, to create necessary, by contents and configuration, vascularized complexes of tissues, is applied for effective treatment of complex defects in tissues. In experiment on laboratory animals for prelamination of vascularized flaps were applied separate and combined placement of mucosal and cartilaginous autotransplants. Results of the investigation witness possibility and efficacy of creation of content--component complexes of tissues, owing necessary characteristics for their further application in the clinic during performance of reconstructive interventions.

[Neovascularisation and free microsurgical transfer of cartilage-engineered constructs]. / Neovaskularisation und freier mikrochirurgischer Transfer von in vitro gezüchteten Knorpelkonstrukten.

BACKGROUND: Clinical imperatives for new cartilage to replace or restore the function of traumatized or missing tissue as a consequence of trauma, inherent malformations or disease has led to the need for therapies or procedures to generate cartilage for clinical applications. To ensure shape, function, and survival, in vitro cartilage-engineered constructs need to be revascularized. This study presents a viable method for neovascularization and free microsurgical transfer of these in vitro constructs. MATERIAL AND METHODS: Twelve female Chinchilla Bastard rabbits were operated. Cartilage-engineered constructs were created by isolating chondrocytes from auricular biopsies, amplifying in monolayer culture, and then seeding them onto polycaprolactone scaffolds. In each prefabricated skin flap, three in vitro cartilage-engineered constructs measuring 2×2×0.5 cm and one construct without cells, which served as the control, were implanted beneath an 8×15-cm random-pattern skin flap, neovascularized by implantation of an arteriovenous vascular pedicle with maximal blood flow. After 6 weeks, the neovascularized flaps with embedded cartilage-engineered constructs were completely removed based on the newly implanted vascular pedicle, and then freely retransferred into position using microsurgery. Macroscopic observation, histology, selective microangiography, and immunohistochemistry were performed to determine the construct vitality, neovascularization, and new cartilage formation. RESULTS: All neovascularized skin flaps with embedded tissue-engineered cartilage constructs were effectively free-transferred as free flaps. The implanted constructs were protected and well integrated within the flap. All constructs were well neovascularized and showed histologically stability in both form and size. Immunohistology showed the existence of cartilage-like tissue with extracellular matrix neosynthesis. CONCLUSION: Our experimental study revealed the reliable ability of neovascularization and free microsurgical transplantation of cartilage-engineered constructs using prefabricated flaps. With respect to effective clinical application, engineered cartilage composed of a patient's own cells can become a feasible option for the reconstruction of large cartilage defects or auricular reconstruction using this method. The procedure also represents a promising alternative for clinical practice due to minimal donor site morbidity and favorable aesthetic outcomes.

Venous drainage from the developing human base of mandible including Meckel's cartilage: the so-called Serres' vein revisited.

PURPOSE: The present study describes the venous drainage, especially, that via the so-called Serres' vein, from border areas between two different types of ossifications: the endochondral ossification of Meckel's cartilage in close topographical relation with the membranous ossification of the mandible. METHODS: Frontal and transverse sections of 25 human fetuses between 8 and 16 weeks of post-conception development. All sections were stained with hematoxylin, and eosin and azan. RESULTS: At 9 weeks, a distinct vein (Serres' vein) is seen originating from the endochondral ossification of Meckel's cartilage. At 11 weeks, the vein collects blood sinusoids from both the endochondral and membranous ossification areas. At 12 weeks the vein accompanies a definite bony canal, the Serres' canal. The vein does not extend anteriorly beyond a level of the deciduous canine germ that was located anterior to the mental foramen. Notably, up to 12 weeks, the vein becomes clearly isolated from the inferior alveolar nerve, artery, and vein. CONCLUSION: Serres' vein seems to be a unique drainage route of ossification, not of the tooth germ, and is similar to veins at the usual diaphysis of a long bone. Although the Serres' canal had been termed "canal of the deciduous dentition", there appears to be no topographical relation with deciduous germs.

[Angiogenesis in cartilage tumors]. / Angiogenese in Knorpeltumoren.

In contrast to normal cartilage, which is avascular, angiogenesis is characteristic of cartilage tumors. In this review, we outline the basic principles of angiogenesis with regard to recent findings on differential morphological and molecular aspects of angiogenesis in cartilage tumors, including enchondromas, conventional chondrosarcomas and dedifferentiated chondrosarcomas. Furthermore, we describe the effects of hypoxia and interleukin-1ß on angiogenic signaling in chondrosarcoma cells.

[Bone and joint diseases in children. Etiology and pathogenesis of osteochondral lesions in children. Osteochondritis dissecans and osteochondrosis].

Osteochondral lesions in children mainly occur in the physeal and epiphyseal cartilage. Osteochondritis dissecans and osteochondrosis (apophysitis) are common and clinically important chronic disorders. These etiology and pathogenesis have also been well investigated in the Veterinary medicine in recent years. One of the most likely causes is proposed as a failure of blood supply to growth cartilage and following focal disturbance of endochondral ossification. Mechanical stress, trauma, rapid growth, anatomic conformation, and dietary imbalances would modify this initial step and break down the normal structure. In human, above-mentioned pathological changes can be detected using recent MRI technology, which contribute quite much in the early diagnosis of lesions in clinic. Another problem in children is acute traumatic growth plate injury, which increases the risk of the early closure of growth plate and following deformity of bone and joint. Early diagnosis and precise treatment are extremely important for children to prevent residual deformity and pain and growth disturbance. In future, less-invasive as well as effective treatments for the focally disturbed or accelerated ossification should be developed.