Long

The role of IL-6 in bone marrow (BM)-derived mesenchymal stem cells (MSCs) proliferation and chondrogenesis

Rheumatoid arthritis (RA) is the most common degenerative arthritic cartilage and represents a disease where the prospect of stem cell therapy offers considerable hope. Currently, bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs) for cell therapy. In the pathology of RA, the pro-inflammatory cytokines, such as interleukin 6 (IL-6) play a pivotal role. To investigate the direct role of IL-6 in the chondrogenic differentiation of murine MSCs (mMSCs), we isolate MSCs from the murine bone marrow, and induce MSCs chondrogenesis with different concentrations of IL-6 in vitro. Through detecting the histological and histochemical qualities of the aggregates, we demonstrate that IL-6 inhibited the differentiation of MSCs into chondrocytes in the dose-dependence manner. These findings suggest that possible strategies for improving the clinical outcome of cartilage repair procedures.

Temporal–spatial expression of ENOLASE after acute spinal cord injury in adult rats

ENOLASE enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recent accumulation of evidence revealed that, in addition to its glycolytic function, enolase is also associated with ischemia, hypoxia and to be a neurotrophic factor. To analysis the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of ENOLASE after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of enolase in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of enolase expression in proliferating microglia and astrocytes. Our data suggest that enolase may be implicated in the proliferation of microglia and astrocytes after SCI.

Dynamic Changes of Jab1 and p27kip1 Expression in Injured Rat Sciatic Nerve

Jun activation domain-binding protein (Jab1) is a multifunctional protein that participates in affecting signaling pathway, controlling cell proliferation and apoptosis, and regulating genomic instability and DNA repair, and acts as a key subunit of COP9 signalosome. p27kip1, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors, was shown to inhibit the enzymatic activity of cyclin–CDK complexes, resulting in cell-cycle arrest at G1. Recent studies have shown that Jab1 directly binds to p27kip1 and induces nuclear export and subsequent degradation in a variety of human cancers, while the association and function of Jab1 and p27kip1 in nervous system lesion and regeneration remain unclear. Here, we performed a sciatic nerve injury model in adult rats and studied the dynamic changes of Jab1 and p27kip1 expression by Western blot. Sciatic nerve crush (SNC) resulted in a significant upregulation of Jab1 and a downregulation of p27kip1. Besides, we observed that Jab1 was expressed widely in Schwann cells (SCs) and had few co-localization in axons by double immunofluorescence staining. In addition, the peak expression of Jab1 was parallel with proliferating cell nuclear antigen (PCNA), and numerous SCs expressing Jab1 were PCNA-positive. Results obtained by co-immunoprecipitation and double labeling further showed their interaction in the sciatic nerve. Thus, these results suggested that Jab1 and p27kip1 may be involved in the pathophysiology of sciatic nerve after SNC.

Temporal and Spatial Expression of KIF3B after Acute Spinal Cord Injury in Adult Rats

The KIF3 subunit KIF3B was proved to be associated with mitosis. It has been known to be engaged in intracellular transport of neurons. To elucidate the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of KIF3B after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of KIF3B in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of KIF3B expression in proliferating microglia and astrocytes. Our data suggest that KIF3B may be implicated in the proliferation of microglia and astrocytes after SCI.The KIF3 subunit KIF3B was proved to be associated with mitosis. It has been known to be engaged in intracellular transport of neurons. To elucidate the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of KIF3B after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of KIF3B in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of KIF3B expression in proliferating microglia and astrocytes. Our data suggest that KIF3B may be implicated in the proliferation of microglia and astrocytes after SCI.

Temporal-Spatial Expressions of Spy1 in Rat Sciatic Nerve After Crush

As a novel cell cycle protein, Spy1 enhances cell proliferation, promotes the G1/S transition as well as inhibits apoptosis in response to UV irradiation. Spy1 levels are tightly regulated during mammary development, and overexpression of Spy1 accelerates tumorigenesis in vivo. But little is known about the role of Spy1 in the pathological process of damage and regeneration of the peripheral nervous system. Here we established a rat sciatic nerve crush (SNC) model to examine the spatiotemporal expression of Spy1. Spy1 expression was elevated gradually after sciatic nerve crush and peaked at day 3. The alteration was due to the increased expression of Spy1 in axons and Schwann cells after SNC. Spy1 expression correlated closely with Schwann cells proliferation in sciatic nerve post injury. Furthermore, Spy1 largely localized in axons in the crushed segment, but rarely co-localized with GAP43. These findings suggested that Spy1 participated in the pathological process response to sciatic nerve injury and may be associated with Schwann cells proliferation and axons regeneration.

Dynamic Change of Prohibitin2 Expression in Rat Sciatic Nerve After Crush

As a novel cell cycle inhibitor, PHB2 controls the G1/S transition in cycling cells in a complex manner. Its aberrant expression is closely related to cell carcinogenesis. While its expression and role in peripheral nervous system lesion and repair were still unknown. Here, we performed an acute sciatic nerve crush (SNC) model in adult rats to examine the dynamic changes of PHB2. Temporally, PHB2 expression was sharply decreased after sciatic nerve crush and reached a valley at day 5. Spatially, PHB2 was widely expressed in the normal sciatic nerve including axons and Schwann cells. While after injury, PHB2 expression decreased predominantly in Schwann cells. The alteration was due to the decreased expression of PHB2 in Schwann cells after SNC. PHB2 expression correlated closely with Schwann cells proliferation in sciatic nerve post injury. Furthermore, PHB2 largely localized with GAP43 in axons in the crushed segment. Collectively, we suggested that PHB2 participated in the pathological process response to sciatic nerve injury and may be associated with Schwann cells proliferation and axons regeneration.

Spatiotemporal patterns of Gem expression after rat spinal cord injury

Gem is an atypical protein of the Ras superfamily that plays a role in regulating voltage-gated Ca(2+) channels and cytoskeletal reorganization. To elucidate the certain expression and biological function in central nervous system (CNS), we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis showed a marked up-regulation of Gem after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of Gem in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen (PCNA) and phenotype-specific markers indicated increases of Gem expression in proliferating microglia and astrocytes. Our data suggest that Gem may be implicated in the proliferation of microglia and astrocytes after SCI.