Symptomatic versus Asymptomatic Intervertebral Disc Degeneration: Is Inflammation the Key?

Degenerated intervertebral discs (d-IVDs) contribute to low back pain (LBP) and are highly common. While some d-IVDs cause discogenic LBP, others are pain-free. Understanding the differences in pathophysiology between painful and pain-free intervertebral disc degeneration (IDD), especially the pathogenic signaling involved in the regulation of painful d-IVDs, is vital for achieving satisfactory effects in clinical treatment. In this review, we revisit recent findings on the detection of inflammatory factors in d-IVDs and summarize the differences between d-IVDs that are painful and those that are pain-free. We postulate that persistent inflammation and innervation are the key factors distinguishing those that are symptomatic and those that are not. This highlights the necessity to use painful, rather than pain-free, degenerated discs in the mechanistic study of disc degeneration and in the development of regenerative approaches, to avoid false positive/negative outcomes. Based on previous molecular d-IVD studies, we also postulate the signaling events from disc overload/ injury to discogenic pain. Although these proposed events are supported by experimental findings, many details about how they are interconnected are not addressed and therefore require experimental investigation.

Concise review: the surface markers and identity of human mesenchymal stem cells.

The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo.

Species variation in the spontaneous calcification of bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) hold great promise for tissue regeneration. With increasing numbers of clinical trials, the safety of BM-MSCs attracts great interest. Previously, we determined that rat BM-MSCs possessed spontaneous calcification without osteogenic induction after continuous culture. However, it is unclear whether BM-MSCs from other species share this characteristic. In this study, spontaneous calcification of BM-MSCs from rat, goat, and human specimens was investigated in vitro. BM-MSCs were cultured in complete medium, and calcification was determined by morphologic observation and alizarin red staining. It was demonstrated that rat BM-MSCs possessed a typically spontaneous calcification, whereas goat and human BM-MSCs under the same system proliferated significantly but did not calcify spontaneously. The significant species variation in spontaneous calcification of BM-MSCs described in this study provides useful information regarding evaluation of numerous BM-MSC-based approaches for bone regeneration and the safety of BM-MSCs.

Molecular analyses of HLA-DRB1, -DPB1, and -DQB1 in Jing ethnic minority of Southwest China.

In the present study, DNA typing for HLA-DRB1, DQB1 and DPB1 was performed using polymerase chain reaction-sequencing based typing (PCR-SBT) method in 144 random selected Jing ethnic individuals inhabiting in South China. Allele frequencies and two-locus haplotypes (DRB1-DQB1) were statistically analyzed and 20 DPB1 alleles, 27 DRB1 and 20 DQB1 were detected. The most frequent DPB1 allele was DPB1*0501 with the percentage of 36.9% followed by DPB1*1301 (15.7%), DPB1*0401 (11.0%) and DPB1*020102 (9.8%). Among the 27 detected DRB1 alleles, DRB1*120201 (13.8%) was most commonly observed followed by DRB1*150201, *030101 and *090102 alleles with the frequencies of 9.4%, 9.1% and 8.3%, respectively. Among the 20 detected DQB1 alleles the most predominant one was DQB1*030101/0309 (19.9%). DQB1*050201 (19.1%), DQB1*0201/0202 (16.1%) and DQB1*050101 (12.3%) were also frequently observed in Jing population. Statistical analysis of two-locus haplotypes showed that DRB1*120201-DQB1*030101/DRB1*120201-DQB1*0309 (HF = 9.4%, D = 6.65x10(-2)) was most predominant followed by DRB1*030101-DQB1*0201/DRB1*030101-DQB1*0202 (HF = 8.1%, D = 6.66 x 10(-2)). The comparison of HLA class II allele and haplotype frequencies in Jing with those in other populations all over the world and a dendrogram based on the DRB1, DQB1 and DPB1 genes suggested that Jing ethnic population has an origin of Southeast Asia and is belonged to the southern group of Chinese populations.