Pediatrics Commons^™

Low Birth Weight Male Guinea Pig Offspring Display Increased Visceral Adiposity In Early Adulthood., Ousseynou Sarr, Jennifer A Thompson, Lin Zhao, Ting-Yim Lee, Timothy Regnault

Paediatrics Publications

Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR) expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery ablation) male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at …

Loss Of Atrx Does Not Confer Susceptibility To Osteoarthritis, Lauren A. Solomon, Bailey A. Russell, David Makar, Nathalie G. Bérubé, Frank Beier

Paediatrics Publications

The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX …

The Centre Of The Brain: Topographical Model Of Motor, Cognitive, Affective, And Somatosensory Functions Of The Basal Ganglia, Marie Arsalidou, Emma G. Duerden, Margot J. Taylor

Paediatrics Publications

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes …

Techniques For The Isolation Of High-Quality Rna From Cells Encapsulated In Chitosan Hydrogels, Claire Yu, Stuart Young, Valerio Russo, Brian G. Amsden, Lauren E. Flynn

Paediatrics Publications

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In …

Gsk-3Β Function In Bone Regulates Skeletal Development, Whole-Body Metabolism, And Male Life Span, J. R. Gillespie, J. R. Bush, G. I. Bell, L. A. Aubrey, H. Dupuis, F. Ferron, B. Kream, G. Dimattia, S. Patel, J. R. Woodgett, G. Karsenty, D. A. Hess, F. Beier

Paediatrics Publications

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of …

Development Of Uv/Hplc Methods For Quantitative Analysis Of Benznidazole In Human Plasma And Urine For Application In Pediatric Clinical Studies, María Elena Marsón, Diego Dante Dana, Jaime Altcheh, Facundo García-Bournissen, Guido Mastrantonio

Paediatrics Publications

Objective: Chagas disease constitutes a major public health problem in Latin America. Correctly designed pharmacokinetic, safety, and bioequivalence studies are desirable in order to fill the knowledge gaps that presently exist on available drugs. It is necessary to develop accurate, simple, reproducible, and sensitive high-performance liquid chromatography (HPLC)/UV methods for the quantization of benznidazole (BNZ) in human plasma and urine for clinical applications, specially in pediatric patients. Methods: Quantization of BNZ in human plasma involved freeze-drying and re-suspension in organic solvent followed by reverse phase HPLC with UV detection. Analysis of BNZ in urine involved liquid/liquid extraction followed by reverse …

Β-Estradiol-Dependent Activation Of The Jak/Stat Pathway Requires P/Cip And Carm1, N. Coughlan, G. Thillainadesan, J. Andrews, M. Isovic, J. Torchia

Paediatrics Publications

The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 (CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/CARM1 complex. Following E2-treatment, histone …

Maternal Taurine Supplementation In Rats Partially Prevents The Adverse Effects Of Early-Life Protein Deprivation On Β-Cell Function And Insulin Sensitivity, Christine Tang, Kelly Marchand, Loretta Lam, Victoria Lux-Lantos, Sandra M. Thyssen, June Guo, Adria Giacca, Edith Arany

Paediatrics Publications

Dietary protein restriction during pregnancy and lactation in rats impairs β-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores β-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of β-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation …

Narrative Medicine As A Means Of Training Medical Students Toward Residency Competencies, Shannon L. Arntfield, Kristen Slesar, Jennifer Dickson, Rita Charon

Paediatrics Publications

Objective: This study sought to explore the perceived influence of narrative medicine training on clinical skill development of fourth-year medical students, focusing on competencies mandated by ACGME and the RCPSC in areas of communication, collaboration, and professionalism. Methods: Using grounded-theory, three methods of data collection were used to query twelve medical students participating in a one-month narrative medicine elective regarding the process of training and the influence on clinical skills. Iterative thematic analysis and data triangulation occurred. Results: Response rate was 91% (survey), 50% (focus group) and 25% (follow-up). Five major findings emerged. Students perceive that they: develop and improve …

Expression Of Ski Can Act As A Negative Feedback Mechanism On Retinoic Acid Signaling, Meaghan A. Melling, Charlotte R.C. Friendship, Trevor G. Shepherd, Thomas A. Drysdale

Paediatrics Publications

Background: Retinoic acid signaling is essential for many aspects of early development in vertebrates. To control the levels of signaling, several retinoic acid target genes have been identified that act to suppress retinoic acid signaling in a negative feedback loop. The nuclear protein Ski has been extensively studied for its ability to suppress transforming growth factor-beta (TGF-β) signaling but has also been implicated in the repression of retinoic acid signaling. Results: We demonstrate that ski expression is up-regulated in response to retinoic acid in both early Xenopus embryos and in human cell lines. Blocking retinoic acid signaling using a retinoic …

How Do Symbolic And Non-Symbolic Numerical Magnitude Processing Skills Relate To Individual Differences In Children's Mathematical Skills? A Review Of Evidence From Brain And Behavior, Bert De Smedt, Marie-Pascale Noël, Camilla Gilmore, Daniel Ansari

Paediatrics Publications

Many studies have tested the association between number magnitude processing and mathematics achievement. However, results appear to be quite different depending on the number format used. When using symbolic numbers (digits), data consistent and robust across studies and populations have been found, with weaker performance associated with weak math achievement and dyscalculia. However, when using non-symbolic format (dots), many conflicting findings are reported. These inconsistencies might be explained by methodological issues. Alternatively, it might be that the processes measured by non-symbolic tasks are not particularly critical for school-relevant mathematics. A few neuroimaging studies have also shown the brain signature of …

The Function Of The Left Angular Gyrus In Mental Arithmetic: Evidence From The Associative Confusion Effect, Roland H. Grabner, Daniel Ansari, Karl Koschutnig, Gernot Reishofer, Franz Ebner

Paediatrics Publications

While the left angular gyrus (lAG) has been repeatedly implicated in mental arithmetic, its precise functional role has not been established. On the one hand, it has been speculated that the lAG is involved in task-specific processes. On the other hand, the observation of relative deactivation during arithmetic has led to the contention that differential lAG activation reflects task-unrelated difficulty effects associated with the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural correlates of the associative confusion effect that allowed us to dissociate effects of task difficulty and task-related arithmetic processes on lAG activation. The …

Umbilical Uptakes And Transplacental Concentration Ratios Of Amino Acids In Severe Fetal Growth Restriction, Timothy R.H. Regnault, Barbra De Vrijer, Henry L. Galan, Randall B. Wilkening, Frederick C. Battaglia, Giacomo Meschia

Paediatrics Publications

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P …

Molecular Mechanisms Underlying Rb Protein Function, Frederick A. Dick, Seth M. Rubin

Paediatrics Publications

Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define …

Microglia-Derived Tnfα Induces Apoptosis In Neural Precursor Cells Via Transcriptional Activation Of The Bcl-2 Family Member Puma, J. Guadagno, X. Xu, M. Karajgikar, A. Brown, S.P. Cregan

Paediatrics Publications

Neuroinflammation is a common feature of acute neurological conditions such as stroke and spinal cord injury, as well as neurodegenerative conditions such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Previous studies have demonstrated that acute neuroinflammation can adversely affect the survival of neural precursor cells (NPCs) and thereby limit the capacity for regeneration and repair. However, the mechanisms by which neuroinflammatory processes induce NPC death remain unclear. Microglia are key mediators of neuroinflammation and when activated to induce a pro-inflammatory state produce a number of factors that could affect NPC survival. Importantly, in the present study we demonstrate …

Conditional Sox9 Ablation Reduces Chondroitin Sulfate Proteoglycan Levels And Improves Motor Function Following Spinal Cord Injury, William M. Mckillop, Magdalena Dragan, Andreas Schedl, Arthur Brown

Paediatrics Publications

Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic …

Susceptibility To Fatty Acid-Induced Β-Cell Dysfunction Is Enhanced In Prediabetic Diabetes-Prone Biobreeding Rats: A Potential Link Between Β-Cell Lipotoxicity And Islet Inflammation, Christine Tang, Anthony E. Naassan, Astrid Chamson-Reig, Khajag Koulajian, Tracy T. Goh, Frederick Yoon, Andrei I. Oprescu, Husam Ghanim, Gary F. Lewis, Paresh Dandona, Marc Y. Donath, Jan A. Ehses, Edith Arany, Adria Giacca

Paediatrics Publications

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth …

Progastrin Stimulates Colonic Cell Proliferation Via Cck2r- And Β-Arrestin-Dependent Suppression Of Bmp2, Guangchun Jin, C. Benedikt Westphalen, Yoku Hayakawa, Daniel L. Worthley, Samuel Asfaha, Xiangdong Yang, Xiaowei Chen, Yiling Si, Hongshan Wang, Yagnesh Tailor, Richard A. Friedman, Timothy C. Wang

Paediatrics Publications

Background & Aims Progastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R) - partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R. Methods We performed microarray analysis to compare changes in gene expression in the colonic mucosa of mice that express a human progastrin transgene, gastrin knockout mice, and C57BL/6 mice (controls); the effects of progastrin were also determined on in vitro colonic crypt …

Mice That Express Human Interleukin-8 Have Increased Mobilization Of Immature Myeloid Cells, Which Exacerbates Inflammation And Accelerates Colon Carcinogenesis, Samuel Asfaha, Alexander N. Dubeykovskiy, Hiroyuki Tomita, Xiangdong Yang, Sarah Stokes, Wataru Shibata, Richard A. Friedman, Hiroshi Ariyama, Zinaida A. Dubeykovskaya, Sureshkumar Muthupalani, Russell Ericksen, Harold Frucht, James G. Fox, Timothy C. Wang

Paediatrics Publications

Background & Aims: Interleukin (IL)-8 has an important role in initiating inflammation in humans, attracting immune cells such as neutrophils through their receptors CXCR1 and CXCR2. IL-8 has been proposed to contribute to chronic inflammation and cancer. However, mice do not have the IL-8 gene, so human cancer cell lines and xenograft studies have been used to study the role of IL-8 in colon and gastric carcinogenesis. We generated mice that carry a bacterial artificial chromosome that encompasses the entire human IL-8 gene, including its regulatory elements (IL-8Tg mice). Methods: We studied the effects of IL-8 expression in APCmin+/- mice …

Localization Of Pain-Related Brain Activation: A Meta-Analysis Of Neuroimaging Data, Emma G. Duerden, Marie Claire Albanese

Paediatrics Publications

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. …

Effects Of Age And Symptomatology On Cortical Thickness In Autism Spectrum Disorders, Krissy A.R. Doyle-Thomas, Emma G. Duerden, Margot J. Taylor, Jason P. Lerch, Latha V. Soorya, A. Ting Wang, Jin Fan, Eric Hollander, Evdokia Anagnostou

Paediatrics Publications

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from …

Dietary Exposures And Allergy Prevention In High-Risk Infants, Edmond S. Chan, Carl Cummings, Mark Feldman, Ruth B. Grimes, Barbara Grueger, Larry B. Pancer, Anne Rowan Legg, Ellen P. Wood, Fabian P. Gorodzinsky, Nestor Cisneros, Janet Roberts, Adelle Atkinson, Zave Chad, Marie Josée Francoeur, Linda Kirste, Douglas Mack, Marie Noel Primeau, Timothy Vander Leek, Wade Watson

Paediatrics Publications

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps …

B.03 Clinical Utility Of Critical Care Eeg Monitoring In A Canadian Paediatric Centre, Saptharishi Lalgudi Ganesan

Data and Test Instruments

No abstract provided.

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

Overexpression Of Pyruvate Dehydrogenase Kinase 1 And Lactate Dehydrogenase A In Nerve Cells Confers Resistance To Amyloid Β And Other Toxins By Decreasing Mitochondrial Respiration And Reactive Oxygen Species Production, Jordan T. Newington, Tim Rappon, Shawn Albers, Daisy Y. Wong, R. Jane Rylett, Robert C. Cumming

Paediatrics Publications

Background: Aerobic glycolysis promotes resistance against Aβ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to Aβ. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of Aβ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic And Environmental Vulnerabilities In Children With Neurodevelopmental Disorders, Annette Karmiloff-Smith, Dean D'Souza, Tessa M. Dekker, Jo Van Herwegen, Fei Xu, Maja Rodic, Daniel Ansari

Paediatrics Publications

One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the developmental and adult approaches with examples from the cognitive and social domains, and we conclude that static models of adult brain lesions cannot be used to account for the dynamics of …

Cystatin C For The Assessment Of Gfr In Neonates With Congenital Renal Anomalies, Guido Filler, Joanne Grimmer, Shih Han Susan Huang, Erika Bariciak

Paediatrics Publications

No abstract provided.

Analysis Of The Mmp-Dependent And Independent Functions Of Tissue Inhibitor Of Metalloproteinase-2 On The Invasiveness Of Breast Cancer Cells, Logan A. Walsh, Mario A. Cepeda, Sashko Damjanovski

Paediatrics Publications

Matrix metalloproteinases (MMPs) are secreted endopeptidases that play an essential role in remodeling the extracellular matrix (ECM). MMPs are primarily active during development, when the majority of ECM remodeling events occurs. In adults, elevated MMP activity has been observed in many pathological conditions such as cancer and osteoarthritis. The proteolytic activity of MMPs is controlled by their natural inhibitors - the tissue inhibitor of metalloproteinases (TIMPs). In addition to blocking MMP-mediated proteolysis, TIMPs have a number of MMP-independent functions including binding to cell surface proteins thereby stimulating signaling cascades. TIMP-2, the most studied member of the family, can both inhibit …

The Systemic Inflammatory Response After Spinal Cord Injury In The Rat Is Decreased By Α4Β1 Integrin Blockade, Feng Bao, Vanessa Omana, Arthur Brown, Lynne C. Weaver

Paediatrics Publications

The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12 h and is sustained for at least 3 days. We have previously shown that blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI. In another study we found that blockade of α4β1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore we considered it important to assess the …

Association Of Cartilage-Specific Deletion Of Peroxisome Proliferator-Activated Receptor Γ With Abnormal Endochondral Ossification And Impaired Cartilage Growth And Development In A Murine Model, Roxana Monemdjou, Faezeh Vasheghani, Hassan Fahmi, Gemma Perez, Meryem Blati, Noboru Taniguchi, Martin Lotz, René St-Arnaud, Jean Pierre Pelletier, Johanne Martel-Pelletier, Frank Beier, Mohit Kapoor

Paediatrics Publications

Objective Long bones develop through the strictly regulated process of endochondral ossification within the growth plate, resulting in the replacement of cartilage by bone. Defects in this process can result in skeletal abnormalities and a predisposition to degenerative joint diseases such as osteoarthritis (OA). Studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is an important therapeutic target in OA. To devise PPARγ-related therapies in OA, it is critical to identify the role of this transcription factor in cartilage biology. Therefore, this study sought to determine the in vivo role of PPARγ in endochondral ossification and …