Biological role of heparan sulfate in osteogenesis: A review.

Heparan sulfate (HS) is extensively expressed in cells, for example, cell membrane and extracellular matrix of most mammalian cells and tissues, playing a key role in the growth and development of life by maintaining homeostasis and implicating in the etiology and diseases. Recent studies have revealed that HS is involved in osteogenesis via coordinating multiple signaling pathways. The potential effect of HS on osteogenesis is a complicated and delicate biological process, which involves the participation of osteocytes, chondrocytes, osteoblasts, osteoclasts and a variety of cytokines. In this review, we summarized the structural and functional characteristics of HS and highlighted the molecular mechanism of HS in bone metabolism to provide novel research perspectives for the further medical research.

Selective regulation of RANKL/RANK/OPG pathway by heparan sulfate through the binding with estrogen receptor ß in MC3T3-E1 cells.

Heparan sulfate (HS) is a linear anionic polysaccharide with repeating sulfated disaccharide units, which has been proven with various regulatory osteogenesis effects through multi-pathway signaling, but its impacts on receptor-activator of nuclear factor kappa beta ligand/receptor-activator of nuclear factor kappa beta/osteoprotegerin (RANKL/RANK/OPG) pathway is still poorly understood. In this study, the binding affinity between HS and estrogen receptor beta (ER-ß) was virtually analyzed using computer simulative docking method and experimentally studied by surface plasmon resonance (SPR). Thereafter, short interfering RNAs (siRNAs) were constructed to deliberately down-regulate the level of ER-ß in MC3T3-E1 cell line, and the transfected and non-transfected osteoblasts displaying good growth conditions were subsequently treated with HS. The results indicated that HS significantly reduced the expression level of RANKL without markedly affecting the expression of decoy receptor OPG during osteoblast differentiation, which can be partially owing to the interaction between HS and ER-ß. Meanwhile, the expression of RANKL in MC3T3-E1 cells was obviously increased after the transfection, demonstrating ER-ß as the key biomarker that regulates RANKL expression. The current work provided important supplementary information on the regulation mechanism of RANKL/RANK/OPG axis by HS.

TRIM58 Interacts with Pyruvate Kinase M2 to Inhibit Tumorigenicity in Human Osteosarcoma Cells.

BACKGROUND: Tripartite motif containing 58 (TRIM58), an E3 ubiquitin ligase, is reported as a suppressor gene in certain human tumors. However, the biological function of TRIM58 in osteosarcoma (OS) is still less identified. METHODS: In the present study, TRIM58 induced silencing and overexpression in OS cells using RNA interference (RNAi) and lentiviral-mediated vector, respectively. Cell proliferation profiles were analyzed using cell counting kit-8 (CCK-8) assay. Cell apoptosis profiles were determined using a flow cytometer. qRT-PCR and western blot were used to determine gene expression. Coimmunoprecipitation (Co-IP) assay was used to examine protein interaction. RESULTS: Our results demonstrated TRIM58 was downregulated in human OS tissues. Overexpression of TRIM58 remarkably suppressed the growth of OS cells and decreased glucose transportation and lactate secretion. These results indicated that TRIM58 involved in the regulation of energy metabolism in OS cells. Importantly, TRIM58 interacted with pyruvate kinase M2 (PKM2) in OS cells. Moreover, TRIM58 might inhibit the activity of PKM2 through enhancing its polyubiquitination in OS cells. CONCLUSIONS: This analysis not only explored a deep understanding of the biological function of TRIM58 but also indicated its signaling pathway in OS cells.

Heparan sulfate loaded polycaprolactone-hydroxyapatite scaffolds with 3D printing for bone defect repair.

With the increasing applications of 3D printing technology in biomedical field, the composition or additives of the related materials has become critical for the next development. In the current study, we have prepared 3D printed polycaprolactone-hydroxyapatite (PCL-HA) porous scaffolds with loaded heparan sulfate (HS), in order to reveal the reparative effect of different concentrations of HS on the healing of bone defects. As a result, the scaffold itself showed sound compression resistance, air porosity and good biocompatibility. From both in vitro and in vivo experiments, the scaffold with low concentration of HS led to positive effects in promoting osteoblast maturation and accelerating bone defect repair. Moreover, scaffold with high concentration of HS showed notable inhibitive effort on the proliferation of osteoblasts, yet it still brought about positive effects in repairing bone defects in organisms. Thus, with good structural properties and biocompatibility, 3D printed PCL-HA-HS composite scaffold can facilitate and accelerate the repairing of biological bone defects, demonstrating as an effective biomaterial for bone defect repair.

Postoperative redislocation of the hip in a patient with congenital insensitivity to pain with anhidrosis: A case report and review of literature.

Pelvic osteotomy is commonly used to adjust acetabula dysplasia for congenital dislocation of the hip, whereas congenital insensitivity to pain with anhidrosis (CIPA) is a rare hereditary disease that often has the characteristics of joint development deformity and easy fracture. This article reports the case involving a CIPA patient who was surgically treated by Chiari pelvic osteotomy and proximal femoral rotation osteotomy for congenital dislocation of the left hip joint and was provided long-term follow-up for redislocation and bilateral femoral head absorption.