Tartrate resistant acid phosphatase (TRAP) was shown to be critical for skeleton development, and TRAP deficiency leads to a reduced resorptive activity during endochondral ossification resulting in an osteopetrotic phenotype and shortened long bones in adult mice. A proper longitudinal growth depends on a timely, well-coordinated vascularization and formation of the secondary ossification center (SOC) of the long bones epiphysis. Our results demonstrate that TRAP is not essential for the formation of the epiphyseal vascular network. Therefore, in wild type (Wt) controls as well as TRAP deficient (TRAP(-/-)) mutants vascularised cartilage canals are present from postnatal day (P) five. However, in the epiphysis of the TRAP(-/-) mice cartilage mineralization, formation of the marrow cavity and the SOC occur prematurely compared with the controls. In the mutant mice the entire growth plate is widened due to an expansion of the hypertrophic zone. This is not seen in younger animals but first detected at week (W) three and during further development. Moreover, an enhanced number of thickened trabeculae, indicative of the osteopetrotic phenotype, are observed in the metaphysis beginning with W three. Epiphyseal excavation was proposed as an important function of TRAP, and we examined whether TRAP deficiency affects this process. We therefore evaluated the marrow cavity volume (MCV) and the epiphyseal volume (EV) and computed the MCV to EV ratio (MCV/EV). We investigated developmental stages until W 12. Our results indicate that both epiphyseal excavation and establishment of the SOC are hardly impaired in the knockouts. Furthermore, no differences in the morphology of the epiphyseal bone trabeculae and remodeling of the articular cartilage layers are noted between Wt and TRAP(-/-) mice. We conclude that in long bones, TRAP is critical for the development of the growth plate and the metaphysis but apparently not for the epiphyseal vascularization, excavation, and establishment of the SOC.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

The bones are of mesenchymal or ectomesenchymal origin, form the skeleton of most vertebrates, and are essential for locomotion and organ protection. As a living tissue they are highly vascularized and remodelled throughout life to maintain intact. Bones consist of osteocytes entrapped in a mineralized extracellular matrix, and via their elaborated network of cytoplasmic processes they do not only communicate with each other but also with the cells on the bone surface (bone lining cells). Bone tissue develops through a series of fine-tuned processes, and there are two modes of bone formation, referred to either as intramembranous or endochondral ossification. In intramembranous ossification, bones develop directly from condensations of mesenchymal cells, and the flat bones of the skull, the clavicles and the perichondral bone cuff develop via this process. The bones of the axial (ribs and vertebrae) and the appendicular skeleton (e.g. upper and lower limbs) form through endochondral ossification where mesenchyme turns into a cartilaginous intermediate with the shape of the future skeletal element that is gradually replaced by bone. Endochondral ossification occurs in all vertebrate taxa and its onset involves differentiation of the chondrocytes, mineralization of the extracellular cartilage matrix and vascularization of the intermediate, followed by disintegration and resorption of the cartilage, bone formation, and finally - after complete ossification of the cartilage model - the establishment of an avascular articular cartilage. The epiphyseal growth plate regulates the longitudinal growth of the bones, achieved by a balanced proliferation and elimination of chondrocytes, and the question whether the late hypertrophic chondrocytes die or transform into osteogenic cells is still being hotly debated. The complex processes leading to endochondral ossification have been studied for over a century, and this review aims to give an overview of the histological and molecular events, arising from the long bones' (e.g. femur, tibia) development. The fate of the hypertrophic chondrocytes will be discussed in the light of new findings obtained from cell tracking studies.

Human spiral ganglion (SG) neurons show remarkable survival properties and maintain electric excitability for a long time after complete deafness and even separation from the organ of Corti, features essential for cochlear implantation. Here, we analyze and compare the localization and distribution of gap junction (GJ) intercellular channels and connexin 43 (Cx43) in cells surrounding SG cell bodies in man and guinea pig by using transmission electron microscopy and confocal immunohistochemistry. GJs and Cx43 expression has been recognized in satellite glial cells (SGCs) in non-myelinating sensory ganglia including the human SG. In man, SG neurons can survive as mono-polar or “amputated” cells with unbroken central projections following dendrite degeneration and consolidation of the dendrite pole. Cx43-mediated GJ signaling between SGCs is believed to play a key role in this “healing” process and could explain the unique preservation of human SG neurons and the persistence of cochlear implant function.

Osteoblasts and osteocytes derive from the same precursors, and osteocytes are terminally differentiated osteoblasts. These two cell types are distinguishable by their morphology, localization and levels of expression of various bone cell‐specific markers. In the present study on the chicken femur we investigated the properties of the mesenchymal cells within cartilage canals on their course into the secondary ossification centre (SOC). We examined several developmental stages after hatching by means of light microscopy, electron microscopy, immunohistochemistry and in situ hybridization. Cartilage canals appeared as extensions of the perichondrium into the developing distal epiphysis and they were arranged in a complex network. Within the epiphysis an SOC was formed and cartilage canals penetrated into it. In addition, they were successively incorporated into the SOC during its growth in the radial direction. Thus, the canals provided this centre with mesenchymal cells and vessels. It should be emphasized that regression of cartilage canals could never be observed in the growing bone. Outside the SOC the mesenchymal cells of the canals expressed type I collagen and periostin and thus these cells had the characteristics of preosteoblasts. Periostin was also expressed by numerous chondrocytes. Within the SOC the synthesis of periostin was down‐regulated and the majority of osteoblasts were periostin negative. Furthermore, osteocytes did not secret this protein. Tissue‐non‐specific alkaline phosphatase (TNAP) staining was only detectable where matrix vesicles were present. These vesicles were found around the blind end of cartilage canals within the SOC where newly formed osteoid started to mineralize. The vesicles originated from osteoblasts as well as from late osteoblasts/preosteocytes and thus TNAP was only expressed by these cells. Our results provide evidence that the mesenchymal cells of cartilage canals express various bone cell‐specific markers depending on their position. We suggest that these cells differentiate from preosteoblasts into osteocytes on their course into the SOC and consider that cartilage canals are essential for normal bone development within the epiphysis. Furthermore, we propose that the expression of periostin by preosteoblasts and several chondrocytes is required for adhesion of these cells to the extracellular matrix.