Growth Arrest-Specific 2 Gene Expression during Patellar Tendon Healing

2003 ◽  
Vol 173 (3) ◽  
pp. 138-146 ◽  
Author(s):  
K.K.H. Lee ◽  
D.Q. Cai ◽  
M.K. Tang ◽  
K.F. Tsang ◽  
W.H. Kwong ◽  
...  
Author(s):  
Nathaniel A. Dyment ◽  
Namdar Kazemi ◽  
Lindsey E. Aschbacher-Smith ◽  
Nicolas J. Barthelery ◽  
Keith Kenter ◽  
...  

Tendon and ligament injuries present a considerable socioeconomic impact as close to 50% of the 32 million musculoskeletal injuries in the US per year include these structures [1]. The inadequate healing in these tissues requires novel treatment modalities. Improving tendon tissue engineering dictates that we better understand the process of natural adult tendon healing. Type-I (Col1) and Type-II (Col2) collagens are important structural proteins in tendon as Col1 is the main collagen type found in the tendon midsubstance while Col2 is expressed at the insertion into bone during development, growth, and healing [2–3]. Expression of Col1 and Col2 has typically been analyzed via qPCR, western blotting, and immunohistochemistry (IHC) during healing. However, the temporal expression of these genes is still poorly understood on a cell-by-cell basis. Our lab has previously studied patellar tendon (PT) healing in NZW rabbits [4]. While the NZW rabbit allows for controlled injuries and accurate biomechanical assessment of healing, it lacks the genetic power that is offered in the mouse. Therefore, pOBCo13.6GFPtpz (Col1) and pCol2ECFP (Col2) double transgenic (DT) reporter mice were created to track spatiotemporal gene expression. Thus, the objectives of this study were to monitor changes in: 1) spatiotemporal Col1 and Col2 gene expression patterns, 2) tissue morphology, and 3) healing biomechanics following a full-length, central PT injury in Col1/Col2 DT mice and to compare these natural healing results to contralateral surgical shams and normal PT in age-matched controls.


Physiology ◽  
1997 ◽  
Vol 12 (6) ◽  
pp. 286-293 ◽  
Author(s):  
JT Neary

Distinct signal transduction cascades comprised of at least three proteinkinases mediate cellular proliferation and differentiation, growth arrest, and programmed cell death. These cytosolic enzymes relay extracellular signals from cell surface to nucleus, leading to changes in gene expression. Signaling components of these cascades offer new possibilities for therapeutic strategies in tumorigenesis, inflammatory diseases, immunopotentiation, wound healing, and regeneration.


2007 ◽  
Vol 13 (6) ◽  
pp. 1219-1226 ◽  
Author(s):  
Natalia Juncosa-Melvin ◽  
Karl S. Matlin ◽  
Robert W. Holdcraft ◽  
Victor S. Nirmalanandhan ◽  
David L. Butler

2018 ◽  
Vol 48 (1) ◽  
pp. 397-408 ◽  
Author(s):  
Ingrid  Felicidade ◽  
Daniele Sartori ◽  
Susan L.M. Coort ◽  
Simone Cristine Semprebon ◽  
Andressa Megumi Niwa ◽  
...  

Background/Aims: Compared with non-obese individuals, obese individuals commonly store more vitamin D in adipose tissue. VDR expression in adipose tissue can influence adipogenesis and is therefore a target pathway deserving further study. This study aims to assess the role of 1,25(OH)2D3 in human preadipocyte proliferation and differentiation. Methods: RTCA, MTT, and trypan blue assays were used to assess the effects of 1,25(OH)2D3 on the viability, proliferation, and adipogenic differentiation of SGBS cells. Cell cycle and apoptosis analyses were performed with flow cytometry, triglycerides were quantified, and RT-qPCR was used to assess gene expression. Results: We confirmed that the SGBS cell model is suitable for studying adipogenesis and demonstrated that the differentiation protocol induces cell maturation, thereby increasing the lipid content of cells independently of treatment. 1,25(OH)2D3 treatment had different effects according to the cell stage, indicating different modes of action driving proliferation and differentiation. In preadipocytes, 1,25(OH)2D3 induced G1 growth arrest at both tested concentrations without altering CDKN1A gene expression. Treatment with 100 nM 1,25(OH)2D3 also decreased MTT absorbance and the lipid concentration. Moreover, increased normalized cell index values and decreased metabolic activity were not induced by proliferation or apoptosis. Exposure to 100 nM 1,25(OH)2D3 induced VDR, CEBPA, and CEBPB expression, even in the preadipocyte stage. During adipogenesis, 1,25(OH)2D3 had limited effects on processes such as VDR and PPARG gene expression, but it upregulated CEBPA expression. Conclusions: We demonstrated for the first time that 1,25(OH)2D3 induces changes in preadipocytes, including VDR expression and growth arrest, and increases the lipid content in adipocytes treated for 16 days. Preadipocytes are important cells in adipose tissue homeostasis, and understanding the role of 1,25(OH)2D3 in adipogenesis is a crucial step in ensuring adequate vitamin D supplementation, especially for obese individuals.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Borys Frankewycz ◽  
Daniel Cimino ◽  
Nelly Andarawis-Puri

Abstract Background Tendon injuries are common musculoskeletal injuries that heal with scar tissue formation, often achieving reduced biomechanical and functional properties. The murine patellar tendon is a research tool that holds potential for investigating tendon healing and can be useful for exploring therapeutic strategies. Since healing is a complex process that results from the collaboration between the systemic and local tissue environment, a murine tendon transplantation model that can be applied to transgenic mice and genetic mutants would allow isolation of systemic versus local tendon factors in driving effective tendon healing. Preliminary studies have shown that transplantation with simple tendon sutures results in a proximalization of the patellar bone due to the involuntary quadriceps muscle force leading to tearing of the graft and failure of the knee extensor mechanism. To avoid this elongation of the graft, two cerclage techniques for murine patellar tendon transplantation were introduced and validated. Methods Three developed surgical techniques (no-cerclage-augmentation (NCA)), transfascial suture cerclage with encirclement of the patellar tendon (TFSC), and dual-cerclage-augmentation with a transosseous bone-to-bone cerclage through the patella bone and an additional musculotendinous cerclage (DCA)) were compared at 4 and 8 weeks macroscopically in regards to graft continuity, cerclage integrity, gap formation, and radiologically by measuring the patello-tibial distance and using a patella bone position grading system. Results The NCA group showed complete failure at 5–7 days after surgery. The TFSC has led to 69% functional failure of the cerclage. In contrast, the DCA with a has led to 78% success with improvement in patellar bone position and a similar patello-tibial distance to the naïve contralateral murine knees over the time period of 8 weeks. Conclusions This study shows that a bone-to-bone cerclage is necessary to maintain a desired graft length in murine patellar tendon models. This surgery technique can serve for future graft trans- and implantations in the murine patellar tendon.


2016 ◽  
Vol 215 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Katherine M. Aird ◽  
Osamu Iwasaki ◽  
Andrew V. Kossenkov ◽  
Hideki Tanizawa ◽  
Nail Fatkhutdinov ◽  
...  

Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear. In this study, we report that high mobility group box 2 (HMGB2) orchestrates the chromatin landscape of SASP gene loci. HMGB2 preferentially localizes to SASP gene loci during senescence. Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlates with incorporation of SASP gene loci into SAHF. Our results establish HMGB2 as a novel master regulator that orchestrates SASP through prevention of heterochromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment during senescence.


Cytokine ◽  
2011 ◽  
Vol 53 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Begoña Santiago ◽  
Esther Calonge ◽  
Manuel J. Del Rey ◽  
Irene Gutierrez-Cañas ◽  
Elena Izquierdo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document