Osteonecrosis of the Femoral Head in an Adolescent on Long-Term Inhalational Corticosteroids.

A relationship between the development of osteonecrosis of the femoral head and systemic corticosteroids has been well established in the literature, particularly in adults. However, the link between osteonecrosis and inhaled corticosteroids is less researched and understood. We report an usual case report of a 10-year-old male who developed ipsilateral femoral head osteonecrosis after long-term inhalational corticosteroid and intermittent short courses of oral steroid usage with a unique presentation and delayed diagnosis.

Postinjection Muscle Fibrosis from Lupron.

We describe the case of a 6.5-year-old girl with central precocious puberty (CPP), which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP.

Leptin Antagonizes Peroxisome Proliferator-Activated Receptor-γ Signaling in Growth Plate Chondrocytes.

Leptin is an obesity-associated cytokine-like hormone encoded by the ob gene. Recent studies reveal that leptin promotes proliferation and differentiation of chondrocytes, suggesting a peripheral role of leptin in regulating growth plate function. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcriptional regulator of adipogenesis.

Activation of Wnt Planar Cell Polarity (PCP) signaling promotes growth plate column formation in vitro.

Disrupting the Wnt Planar Cell Polarity (PCP) signaling pathway in vivo results in loss of columnar growth plate architecture, but it is unknown whether activation of this pathway in vitro is sufficient to promote column formation. We hypothesized that activation of the Wnt PCP pathway in growth plate chondrocyte cell pellets would promote columnar organization in these cells that are normally oriented randomly in culture. Rat growth plate chondrocytes were transfected with plasmids encoding the Fzd7 cell-surface Wnt receptor, a Fzd7 deletion mutant lacking the Wnt-binding domain, or Wnt receptor-associated proteins Ror2 or Vangl2, and then cultured as three-dimensional cell pellets in the presence of recombinant Wnt5a or Wnt5b for 21 days.

Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes.

The transcription factor Sox9 is necessary for early chondrogenesis, but its subsequent roles in the cartilage growth plate, a highly specialized structure that drives skeletal growth and endochondral ossification, remain unclear. Using a doxycycline-inducible Cre transgene and Sox9 conditional null alleles in the mouse, we show that Sox9 is required to maintain chondrocyte columnar proliferation and generate cell hypertrophy, two key features of functional growth plates. Sox9 keeps Runx2 expression and β-catenin signaling in check and thereby inhibits not only progression from proliferation to prehypertrophy, but also subsequent acquisition of an osteoblastic phenotype.

Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals.

Leptin synergizes with thyroid hormone signaling in promoting growth plate chondrocyte proliferation and terminal differentiation in vitro.

Leptin and thyroid hormone are two hormones that regulate energy balance through central signaling mechanisms. Recent studies in leptin-deficient ob/ob mice indicate that leptin also has peripheral effects in modulating the function of the growth plate, perhaps in terms of proliferation and differentiation enhancement. Thyroid hormone has been well-described as a potent stimulator of growth plate chondrocyte maturation.

Thyroid hormone-mediated growth and differentiation of growth plate chondrocytes involves IGF-1 modulation of beta-catenin signaling.

Thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through modulation of the Wnt/beta-catenin signaling pathway. Insulin-like growth factor 1 (IGF-1) has been described as a stabilizer of beta-catenin, and thyroid hormone is a known stimulator of IGF-1 receptor expression. The purpose of this study was to test the hypothesis that IGF-1 signaling is involved in the interaction between the thyroid hormone and the Wnt/beta-catenin signaling pathways in regulating growth plate chondrocyte proliferation and differentiation.

Carboxypeptidase Z (CPZ) links thyroid hormone and Wnt signaling pathways in growth plate chondrocytes.

Carboxypeptidase Z (CPZ) removes carboxyl-terminal basic amino acid residues, particularly arginine residues, from proteins. CPZ contains a cysteine-rich domain (CRD) similar to the CRD found in the frizzled family of Wnt receptors. We have previously shown that thyroid hormone regulates terminal differentiation of growth plate chondrocytes through activation of Wnt-4 expression and Wnt/beta-catenin signaling.

Thyroid hormone interacts with the Wnt/beta-catenin signaling pathway in the terminal differentiation of growth plate chondrocytes.

Unlabelled: Thyroid hormone activates Wnt-4 expression and Wnt/beta-catenin signaling in rat growth plate chondrocytes. Wnt antagonists Frzb/sFRP3 and Dkk1 inhibit T3-induced Wnt/beta-catenin activation and inhibit the maturation-promoting effects of T3 in growth plate cells. This study indicates that thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through modulating Wnt/beta-catenin signaling.

Closed reduction for treatment of development dysplasia of the hip in children.

Although many studies have analyzed the success rates of closed reduction and spica casting for the treatment of developmental dysplasia of the hip (DDH) in children, the definition of success for this procedure is not standardized in the literature. We retrospectively reviewed our experience with closed reduction for treatment of DDH in 30 children (35 hips) over an 8-year period to determine the success rates of this procedure on the basis of how success is defined. In only 1 patient (2 hips, 6%) were the hips unable to be concentrically reduced with sufficient stability at the time of closed reduction.

Closed reduction for treatment of developmental dysplasia of the hip in children.

Although many studies have analyzed the success rates of closed reduction and spica casting for the treatment of developmental dysplasia of the hip (DDH) in children, the definition of success for this procedure is not standardized in the literature. We retrospectively reviewed our experience with closed reduction for treatment of DDH in 30 children (35 hips) over an 8-year period to determine the success rates of this procedure on the basis of how success is defined. In only 1 patient (2 hips, 6%) were the hips unable to be concentrically reduced with sufficient stability at the time of closed reduction.

Peroxisome Proliferator-Activated Receptor-gamma Promotes Adipogenic Changes in Growth Plate Chondrocytes In Vitro.

Chondrocytes and adipocytes are two differentiated cell types which are both derived from mesenchymal cells. The purpose of this study was to investigate whether peroxisome proliferator-activated receptor-gamma (PPARgamma), a transcription factor involved in lineage determination during adipogenesis, is able to induce adipogenic differentiation in growth plate chondrocytes. Isolated epiphyseal chondrocytes were infected with a PPARgamma adenovirus or treated with the PPARgamma agonist ciglitazone.

Thyroid hormone and the growth plate.

Thyroid hormone was first identified as a potent regulator of skeletal maturation at the growth plate more than forty years ago. Since that time, many in vitro and in vivo studies have confirmed that thyroid hormone regulates the critical transition between cell proliferation and terminal differentiation in the growth plate, specifically the maturation of growth plate chondrocytes into hypertrophic cells. However these studies have neither identified the molecular mechanisms involved in the regulation of skeletal maturation by thyroid hormone, nor demonstrated how the systemic actions of thyroid hormone interface with the local regulatory milieu of the growth plate.

Analysis of gene expression in mineralized skeletal tissues by laser capture microdissection and RT-PCR.

The analysis of gene expression by growth plate chondrocytes in vivo has been hampered by the inherent difficulty in performing in situ hybridization on mineralized tissues. The combination of laser capture microdissection and reverse transcription-polymerase chain reaction (RT-PCR) allows analysis of gene expression by cells selectively removed from histologic sections by laser ablation. In order to apply this method to mineralized tissues, a decalcification process is required.

Peroxisome proliferator activated receptor-gamma (PPARgamma) represses thyroid hormone signaling in growth plate chondrocytes.

Peroxisome proliferator activated receptors (PPARs) are DNA-binding nuclear hormone receptors that are upregulated in response to high fat diets. PPARs are structurally related to the type II nuclear receptors, including the thyroid hormone receptors (TRs). To investigate if PPARs modulate TR-mediated terminal differentiation of growth plate chondrocytes, primary cultures of epiphyseal chondrocytes transiently transfected with TRalpha and PPARgamma expression vectors were treated with the PPAR ligands ciglitazone or troglitazone.

Expression and activation of peroxisome proliferator-activated receptors in growth plate chondrocytes.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear hormone receptor that is involved in a wide range of cellular processes. Although it is known that PPAR-gamma plays an important role in cell cycle control, inflammation, apoptotic cell death, and other cellular processes, the role of PPAR-gamma in the normal and pathological function of growth plate chondrocytes has not been investigated. The purpose of this study was to determine if PPARs are expressed in growth plate chondrocytes and to describe the biological effect of PPAR activation in these cells.

Expression and activity of the CDK inhibitor p57Kip2 in chondrocytes undergoing hypertrophic differentiation.

Unlabelled: Growth plates of p57-null mice exhibit several abnormalities, including loss of collagen type X (CollX) expression. The phenotypic consequences of p57 expression were assessed in an in vitro model of hypertrophic differentiation. Adenoviral p57 expression was not sufficient for CollX expression but did augment induction of CollX by BMP-2.

Physiology and pathophysiology of the growth plate.

Longitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate. Through a sequential process of cell proliferation, extracellular matrix synthesis, cellular hypertrophy, matrix mineralization, vascular invasion, and eventually apoptosis, the cartilage model is continually replaced by bone as length increases. The regulation of longitudinal growth at the growth plate occurs generally through the intimate interaction of circulating systemic hormones and locally produced peptide growth factors, the net result of which is to trigger changes in gene expression by growth plate chondrocytes.

Second cervical vertebrae pedicle fractures versus synchondrosis in a child.

Fractures of the second cervical vertebrae (C2) can be difficult to diagnose in young children. A 17-month-old infant sustained bilateral C2 pedicle fractures after minor trauma. The initial lateral radiograph showed pedicle defects, but even with computed tomography and a bone scan with single photon emission computed tomography this could not be differentiated from a congenital abnormality.

Sternoclavicular joint ganglion cysts in young children.

Ganglion cysts originating from the sternoclavicular joint in children have not been previously reported. In this study, 5 children who presented with a small mass over the anterior aspect of the sternoclavicular joint were evaluated and treated. Only 1 patient was symptomatic.