Altered IGF-I activity and accelerated bone elongation in growth plates precedes excess weight gain in a mouse model of juvenile obesity

Nearly one-third of children in the United States are overweight or obese by their pre-teens. Tall stature and accelerated bone elongation are characteristic features of childhood obesity, which co-occur with conditions such as limb bowing, slipped epiphyses, and fractures. Obese children paradoxically have normal circulating IGF-I, the major growth-stimulating hormone. Here we describe and validate a mouse model of excess dietary fat to examine mechanisms of growth acceleration in obesity. We used in vivo multiphoton imaging and immunostaining to test the hypothesis that high-fat diet increases IGF-I activity and alters growth plate structure before the onset of obesity. We tracked bone and body growth in male and female C57BL/6 mice (N = 114) on high-fat (60% kcal fat) or control (10% kcal fat) diets from weaning (3-weeks) to skeletal maturity (12-weeks). Tibial and tail elongation rates increased after brief (1-2 week) high-fat diet exposure without altering serum IGF-I. Femoral bone density and growth plate size were increased, but growth plates were disorganized in not-yet-obese high-fat diet mice. Multiphoton imaging revealed more IGF-I in the vasculature surrounding growth plates of high-fat diet mice, and increased uptake when vascular levels peaked. High-fat diet growth plates had more activated IGF-I receptors and fewer inhibitory binding proteins, suggesting increased IGF-I bioavailability in growth plates. These results, which parallel pediatric growth patterns, highlight the fundamental role of diet in the earliest stages of developing obesity-related skeletal complications and validate the utility of the model for future studies aimed at determining mechanisms of diet-enhanced bone lengthening.

Comprehensive expression profiles of mRNAs, lncRNAs and miRNAs in Kashin-Beck disease identified by RNA-sequencing

Kashin-Beck disease (KBD) is a chronic, endemic and deforming osteochondropathy, whose basic pathological alterations include apoptosis and necrosis of chondrocytes in articular cartilage and growth plates and imbalanced extracellular matrix metabolism.

A Comprehensive Review on Acromegaly: A Complicated Endocrine Disorder

Acromegaly is a disease or disorder that is caused by the hyper secretion of growth hormone from the anterior pituitary, that results in the excessive growth of tissues of body and dysfunctioning of other metabolic processes. Acromegaly is usually caused by the non-cancerous (benign) tumour and middle-aged people are mostly affected by it. Patients with acromegaly have pain in the joints, physical deformities, deepening of voice, bulging chest, protruding lower jaw, large feet and hands, oily skin, vision disorder or erectile dysfunction (impotence). Acromegaly occurs after the fusion of growth plates while gigantism occurs before the fusion of growth plates. This article reviews the pathophysiology and management of acromegaly as well as it highlights the etiology and epidemiology of acromegaly

Wdpcp regulates cellular proliferation and differentiation in the developing limb via hedgehog signaling

Background Mice with a loss of function mutation in Wdpcp were described previously to display severe birth defects in the developing heart, neural tube, and limb buds. Further characterization of the skeletal phenotype of Wdpcp null mice was limited by perinatal lethality. Results We utilized Prx1-Cre mice to generate limb bud mesenchyme specific deletion of Wdpcp. These mice recapitulated the appendicular skeletal phenotype of the Wdpcp null mice including polydactyl and limb bud signaling defects. Examination of late stages of limb development demonstrated decreased size of cartilage anlagen, delayed calcification, and abnormal growth plates. Utilizing in vitro assays, we demonstrated that loss of Wdpcp in skeletal progenitors lead to loss of hedgehog signaling responsiveness and associated proliferative response. In vitro chondrogenesis assays showed this loss of hedgehog and proliferative response was associated with decreased expression of early chondrogenic marker N-Cadherin. E14.5 forelimbs demonstrated delayed ossification and expression of osteoblast markers Runx2 and Sp7. P0 growth plates demonstrated loss of hedgehog signaling markers and expansion of the hypertrophic zones of the growth plate. In vitro osteogenesis assays demonstrated decreased osteogenic differentiation of Wdpcp null mesenchymal progenitors in response to hedgehog stimulation. Conclusions These findings demonstrate how Wdpcp and associated regulation of the hedgehog signaling pathway plays an important role at multiple stages of skeletal development. Wdpcp is necessary for positive regulation of hedgehog signaling and associated proliferation is key to the initiation of chondrogenesis. At later stages, Wdpcp facilitates the robust hedgehog response necessary for chondrocyte hypertrophy and osteogenic differentiation.

Hereditary Multiple Exostoses with Ulnar Hemimelia

Hereditary Multiple Exostoses is a skeletal dysplasia that is very rare and defined by formation of numerous cartilage capped benign tumours either pedunculated or sessile known as osteochondromas throughout skeleton especially around the growth plates of ribs, vertebrae, pelvis and long bones. Rarely it can present forearm problems such bowing deformity of radius, ulnar shortening and radiocapitellar dislocation or subluxation. We are presenting a case of 20 year old female who presented with left distal ulnar exostosis resulting in ulnar shortening and radial bowing with restricted supination and pronation range of movement. Other complaint was of multiple non tender bony hard lumps in both upper and lower limbs. Excision of distal ulnar exostosis was done which resulted in marked improvement in pronation and supination range of movement. Hereditary multiple exostoses with forearm deformities though very rare but can present and the treatment is conservative except if any bony swelling manifests any complications such as pain or associated deformity.