Browsing by Author "Jain, D"
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Item Open Access Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids.(Int J Obes (Lond), 2013-08) Wu, C-L; Diekman, BO; Jain, D; Guilak, FINTRODUCTION: Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency and immunophenotype of adult stem cells from a variety of tissues. MATERIALS AND METHODS: Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs) and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet-induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro. RESULTS: Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased platelet-derived growth factor receptor α expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells. CONCLUSIONS: These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.Item Open Access GWAS Identifies New Loci for Painful Temporomandibular Disorder.(J Dent Res, 2017-01-01) Sanders, AE; Jain, D; Sofer, T; Kerr, KF; Laurie, CC; Shaffer, JR; Marazita, ML; Kaste, LM; Slade, GD; Fillingim, RB; Ohrbach, R; Maixner, W; Kocher, T; Bernhardt, O; Teumer, A; Schwahn, C; Sipilä, K; Lähdesmäki, R; Männikkö, M; Pesonen, P; Järvelin, M; Rizzatti-Barbosa, CM; Meloto, CB; Ribeiro-Dasilva, M; Diatchenko, L; Serrano, P; Smith, SBTemporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 10(6)) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10(-8)) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10(-8)) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10(-8)) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10(-7)) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.