ObjectiveTo review the role of vertebral subchondral bone in maintaining normal physiological function of the intervertebral disc and in the intervertebral disc degeneration in light of bone anatomy, microstructure, histopathological features, and MRI imaging features. MethodsThe related home and abroad literature concerning vertebral subchondral bone and intervertebral disc degeneration was extensively reviewed and comprehensively analyzed. ResultsVertebral subchondral bone is part of the vertebral endplate and is defined as the vascularized cortical and trabecular bone layer located between the cartilage endplate and vertebral body. It not only plays a cushion shocks role in terms of conducting stress and effectively resists the hydrostatic nucleus, but also ensures the normal supply of disc nutrition. Subchondral bone sclerosis caused by bone remodeling abnormality severely decreases the ability of subchondral bone stress absorption and protective function of disc, which finally leads to increased inflammatory factors locally and hindered nutrition pathway of disc and enhanced disc degeneration. ConclusionTo further strengthen the knowledge and understanding of the vertebral subchondral bone will play a positive role in the study on the pathogenesis of intervertebral disc degeneration.
Objective To study the expression difference of Sclerostin in the medial and lateral subchondral bone of the varus osteoarthritic knee plateau. Methods The tibial plateau was obtained from 20 patients with varus knee osteoarthritis receiving total knee arthroplasty from March to October 2015. There were 8 males and 12 females with an average age of 67.8 years (range, 61-78 years). The mean course of osteoarthritis was 3.2 years (range, 2-5 years). Before operation, the varus angle was 12.0-25.5° (mean, 17.6°) on the X-ray film. Five cases were rated as grade III and 15 cases as grade IV according to Kellgren-Lawrance classification. Micro-CT scan was performed on the medial and lateral subchondral bone to compare the changes of bone structure; bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure model index (SMI), and the trabecular separation (Tb.Sp) were measured. Immunohistochemistry and real-time fluorescent quantitative PCR were used to test the expressions of Sclerostin protein and sost gene. Results Micro-CT showed that BV/TV, Tb.N, and Tb.Th significantly increased in the medial subchondral bone when compared with the lateral part (P<0.05), but SMI and Tb.Sp significantly reduced (P<0.05). Real-time fluorescent quantitative PCR detection showed that sost gene expression level in the medial subchondral bone (1.000) was significantly lower than that in the lateral part (4.157±2.790) (t=2.371,P=0.040). The percentage of Sclerostin positive cells in the lateral subchondral bone (52.00%±0.19%) was significantly higher than that in the medial subchondral bone (7.20%±0.04%) (t=5.094,P=0.005). Conclusion Sclerostin plays an important role in the subchondral bone remodeling of the varus osteoarthritic knee. And the low expression of Sclerostin may be an important factor to promote bone remodeling and aggravate knee deformity.
ObjectiveTo investigate the effects of icariin (ICA) on serum bone turnover markers expressions and histological changes of cartilage and subchondral bone in mouse osteoarthritis (OA) model.MethodsEighty 8-week-old male C57BL/6J mouse were randomly divided into 8 groups (n=10). The OA model was established by anterior cruciate ligament transaction (ACLT). Group A: sham operation/early-stage normal saline administration; group B: sham operation/early-stage ICA administration; group C: ACLT/early-stage normal saline administration; group D: ACLT/early-stage ICA administration; group E: sham operation/late-stage normal saline administration; group F: sham operation/late-stage ICA administration; group G: ACLT/late-stage normal saline administration; group H: ACLT/late-stage ICA administration. Each animal received either ACLT or simply opening joint capsule, respectively. For groups B and D, ICA was given by gavage [10 mg/(kg·day)] on the first day after ACLT. For groups F and H, ICA was given with the same volume at 4 weeks after operation. The blood serum of the mouse was collected and prepared at 8 weeks after operation. Serum bone turnover markers and cytokines, including C-telopeptide of type I collagen (CTX), osteocalcin (OC), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, were measured by ELISA. Tissue samples from the knee were stained by alcian blue/hematoxylin & orange G (AB/H&OG). Histological changes of cartilage and subchondral bone were observed and evaluated by Osteoarthritis Research Society International (OARSI) scoring system.ResultsComparison between each group with early-stage administration (groups A, B, C, and D): Compared with groups A and B, the levels of CTX and OC in group C were significantly reduced (P<0.05); the levels of IL-6, TNF-α, and IL-1β and OARSI score was significantly increased (P<0.05). Compared with group C, the levels of CTX and OC in group D were significantly increased (P<0.05); the level of IL-6 was significantly reduced (P<0.05); the levels of TNF-α and IL-1β were not changed (P>0.05), and OARSI score was significantly reduced (P<0.05). Histological observation showed that the tibial cartilage loss was significantly improved. Comparison between each group with late-stage administration (groups E, F, G, and H): Compared with groups E and F, the levels of CTX and OC in group G were significantly reduced (P<0.05); the levels of IL-6, TNF-α, and IL-1β and OARSI score were significantly increased (P<0.05). Compared with group G, the level of CTX in group H were increased (P<0.05); the levels of OC, IL-6, TNF-α, and IL-1β and OARSI score were not changed (P>0.05). Histological observation showed that the tibial cartilage loss had no changes after late-stage ICA administration.ConclusionICA plays protective effects on subchondral bone, hyaline, and calcified cartilage. Meanwhile, ICA can improve bone remodeling in subchondral bone of OA to some extent. The consistent changes of serum bone markers and pathological morphology suggest that early intervention of ICA on OA is more effective.
ObjectiveTo summarize the active changes of Wnt signaling pathway in osteoarthritis (OA) as well as the influence and mechanism of dual-targeted regulation on cartilage and subchondral bone and the role of crosstalk between them on OA process.MethodsThe relevant literature concerning the articular cartilage, subchondral bone, and crosstalk between them in OA and non-OA states by Wnt signaling pathway in vivo and vitro experimental studies and clinical studies in recent years was reviewed, and the mechanism was analyzed and summarized.ResultsWnt signaling can regulate the differentiation and function of chondrocytes and osteoblasts through the classic β-catenin-dependent or non-classical β-catenin-independent Wnt signaling pathway and its cross-linking with other signaling pathways, thereby affecting the cartilage and bone metabolism. Moreover, Wnt signaling pathway can activate the downstream protein Wnt1-inducible-signaling pathway protein 1 to regulate the progress of OA and it also can be established gap junctions between different cells in cartilage and subchondral bone to communicate molecules directly to regulate OA occurrence and development. Intra-articular injection of Wnt signaling inhibitor SM04690 can inhibit the progress of OA, and overexpression of Wnt signaling pathway inhibitor Dickkopf in osteoblasts can antagonize the role of vascular endothelial growth factor work on chondrocytes and inhibit the catabolism of its matrix.ConclusionThe regulation of metabolism and function of cartilage and subchondral bone and crosstalk between them is through interactions among Wnt signaling pathway and molecules of other signaling. Therefore, it plays an vital role in the occurrence and development of OA and is expected to become a new target of OA treatment through intervention and regulation of Wnt signaling pathway.