Objective To review the progress of mechanism of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) on normal and osteoarthritis (OA) cartilage and subchondral bones. Methods Recent 1iterature about the effects of PTH and PTHrP on normal and OA cartilage was reviewed. Results PTH and PTHrP can repress the hypertrophic differentiation and apoptosis of chondrocytes and promote their prol iferation, which has a protection effect on chondrocytes of OA; osteoblasts from subchondral bone of OA show a decreased reaction to PTH. Conclusion PTHand PTHrP may delay and protect the progression of OA, which involves in regulating cartilage degeneration and subchondral bone remodl ing through many kinds of signal pathway.
Objective To review the effect of calcitonin on cartilage and subchondral bone of osteoarthritis. Methods Recent l iteratures about the effect of calcitonin on osteoarthritis was reviewed. Results Calcitonin could promotethe synthesis of important cartilage matrix such as proteoglycans and collagen II, propell ing the regeneration of cartilage and subchondral bone. Conclusion Calcitonin can protect articular cartilage through promoting the synthesis of cartilage and inhibiting its degradation.
Objective To review the research progress on protease-activated receptor 2 (PAR-2) in the pathogenesis of osteoarthritis (OA). Methods The relevant literature about the mechanism of PAR-2 in the occurrence and development of OA in recent years was extensively reviewed and comprehensively analyzed. Results Abnormal activation of PAR-2 plays an important role in responses to occurrence and development of OA. Through regulating production and releasing of a variety of cytokines (such as inflammatory factors, metabolic factors, pain factors, etc.), the PAR-2 can involve in pathophysiological progression of OA articular cartilage, subchondral bone, and synovial membrane, as well as occurrence and transmission of pain. Conclusion PAR-2 participation in the development of OA has been confirmed. However, since PAR-2 is complicated and widespread, it is necessary to study the specific role of PAR-2 and the interaction between various signal pathways in the progression of OA, and to elucidate the potential pathophysiological mechanisms of PAR-2 participating in the process of OA, in the hope of exploring the new targets for the effective control of OA.
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.
Objective Simvastatin has been reported to be effective on stimulation of bone formation. To investigate the effects of simvastatin on bone formation relative factors of proximal tibia trabecular bone and on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods Fourty 1-week-old male Sprague Dawley rats were divided randomly into 2 groups, 20 rats per group. Rats in experimental group received subcutaneous injection of simvastatin [(5 mg/ (kg• d)], and the rats in control group received injection of normal sal ine at the same dose. The expressions of bone morphogenetic protein 2 (BMP-2), matrix metalloproteinase 13 (MMP-13), and vascular endothel ial growth factor (VEGF) of trabecular bone were analyzed in the tibia by immunohistochemical staining at 1 and 3 weeks after injection. BMSCs from the rat femur at 1 and 3 weeks after injection were cultured under condition of osteogenic induction. ALP staining wasperformed on the 14th day after culture; real-time fluorescent quantitative PCR was used to detect the mRNA expressions of BMP-2, Runx2, Osterix, Msx2, Dlx3, and Dlx5 on the 21st day after culture; and von Kossa staining was performed on the 28th day after culture. Results There was no significant difference in the expressions of BMP-2, MMP-13, and VEGF betweenthe experimental group and control group at 1 and 3 weeks after injection (P gt; 0.05). There was no significant difference in the percentages of ALP positively-stained cells between the experimental group and the control group on the 14th day after culture (P gt; 0.05). The mRNA expressions of BMP-2, Runx2, Osterix, Msx2, Dlx3, and Dlx5 in osteogenic differentiation-inducedBMSCs had also no significant difference between the experimental group and the control group at 1 and 3 weeks after culture (P gt; 0.05). No significant difference in biomineral ization was found between the experimental group and control group at 1 and 3 weeks after culture (P gt; 0.05). Conclusion Subcutaneous injection of simvastatin [(5 mg/(kg•d)] for 1 or 3 weekscan affect neither the expressions of bone formation relative factors of proximal tibia trabecular bone nor the osteogenic differentiation of the BMSCs.
Objective To investigate the changes in the expression level of PDGF in the bone callus of rats with femoral fracture and brain injury to explore the effect of brain injury on the fracture heal ing and the related mechanism. Methods Sixty-four 12-week-old SD rats weighing (356 ± 25) g were randomly divided into 8 groups with 8 rats in each. The rats in groups A1, B1, C1 and D1 had a femoral fracture and a brain injury for 1, 2, 3 and 4 weeks, respectively; the rats in groups A2, B2, C2 and D2 had a mere fracture without a brain injury for 1, 2, 3 and 4 weeks, respectively. After the CR films were taken, the bone callus was obtained 1, 2, 3 and 4 weeks after operation, respectively. Then, the bone callus and its histology were examined by HE staining, the expressions and changes in the level of PDGF were examined by the immunohistochemical staining, and the level of PDGF mRNA was measured by in situ hybridization. Results The CR films showed that the callus formation in the A1-D1 groups was earl ier and greater than that in the A2-D2 groups at the same time point. The HE staining indicated that more fibroblasts and early-stage chondrocytes were found in group A1; some fibroblasts in the fracture interspace and few early-stage chondrocytes were found in group A2; some newly-formed trabecular bones were found at the end of the fracture in group B1; but no trabecular bone formation was found in group B2; woven bone formation and a few chondrocytes between trabecular bones in the fracture interspace were found in group C1; only a few trabecular bones in the fracture interspace were found in group C2；woven bones turned to lamellar bones in group D1；and more immature trabecular bones in the fracture interspace were found in group D2. The positive expression of PDGF and PDGF mRNA was b in the cytoplasms of fibroblasts, mesenchymal cells, vascular endothel ial cells, early-stage chondrocytes, osteoblasts and osteoclasts. The percentage of the positive cells for PDGF and PDGF mRNA in the callus was significantly higher in groups A1-D1 than in groups A2-D2 at the same time point (P lt; 0.05). Conclusion Brain injury can promote the fracture heal ing process, which is probably related to an increase in the expression level of PDGF after the brain injury.
目的 探讨准分子激光上皮瓣下角膜磨镶术（LASEK）后角膜上皮下雾状混浊（Haze）的形成原因及防治措施。 方法 2004年2月－2011年12月期间采用LASEK治疗近视患者345 例669 只眼，屈光度?3.50～?13.5 D，平均（?6.87 ± 2.92）D；散光?0.50～?4.00 D，平均（?1.83 ± 1.32）D 。根据患者术前屈光等效球镜度数分为：中度近视组（?3.50～?5.75 D）120只眼，高度近视组（?6.00～?8.75 D）288只眼，超高度近视组（?9.00～?13.50 D） 261只眼。应用综合措施防治Haze，术中用日夜配戴的高亲水性绷带型角膜接触镜覆盖保护角膜上皮瓣，术毕频点激素眼液4次，术后使用激素类联合非甾体类抗炎眼液及降眼压药、抗生素眼液；随访6～12个月，观察术后Haze的发生率，并按Fantes（1990）标准分级，分析相关原因。 结果 LASEK术后6个月时0.5级Haze发生率14.65%（98只眼），无1级Haze。各组0.5级Haze发生率分别为中度近视组2.5%（3只眼），高度近视组11.11%（32只眼），超高度近视组24.14%（63只眼）。 结论 LASEK术后Haze的发生与术眼的屈光度呈正比，与角膜上皮瓣的活性和完整性，术后紫外线照射等有关。术后采用激素类联合非甾体类抗炎眼液及降眼压药等综合防治措施，可减少、减轻Haze的发生，使LASEK技术更安全有效。
Objective To investigate the feasibil ity of alendronate (ALN) in treating osteoarthritis (OA) by observing the effects of ALN on interleukin 1β (IL-1β) induced chondrocytes of rat in vitro. Methods The chondrocytes of knee articular surface from 15 SD rats (1-month-old, female or male, weighing 100-150 g) were cultured. The chondrocytes were observed by inverted phase contrast microscope and identified by toluidine blue staining and HE staining. The third passage chondrocytes were divided into 3 groups: the chondrocytes were cultured with DMEM for 5 days in group A, with 10 ng/mL IL-1β for 2 days and with DMEM for 3 days in group B, and with 10 ng/mL IL-1β for 2 days and with 1 × 10-6 mol/L ALN for 3 days in group C. Immunocytochemistry and real-time PCR were performed to determine the expression levels of collagen type II (Col II), matrix metalloproteinase 13 (MMP-13), and β-catenin. Results Toluidine blue staining proved that the cultured cells were chondrocytes. The integrated absorbency (IA) value of Col II in group C (10.290 7 ± 0.499 2) was lower than that in group A (15.377 0 ± 0.571 8) and higher than that in group B (5.463 2 ± 0.450 4), showing significant differences (P lt; 0.05). The IA value of MMP-13 in group C (3.068 6 ± 0.205 6) was significantly lower than that in group B (6.998 1 ± 0.329 7, P lt; 0.05), but there was no significant differenc when compared with group A (2.777 5 ± 0.199 6, P gt; 0.05). The IA value of β-catenin in group C (6.611 7 ± 0.381 8) was lower than that in group B (11.799 9 ± 0.348 7) and higher than that in group A (4.390 3 ± 0.551 9), showing significant differences (P lt; 0.05). The mRNA expression of Col II in group C was significantly higher than those in groups A and B (P lt; 0.05), the mRNA expression of MMP-13 in group C was significantly lower than that in group B (P lt; 0.05) but there was no significant difference when compared with group A (P gt; 0.05). The mRNA expression of β-catenin in group C was significantly lower than that in group B (P lt; 0.05) and higher than that in group A (P lt; 0.05). Conclusion ALN can protect rat chondrocyte from OA induced by IL-1β in vitro possibly by upregulating Col II and inhibiting the expression of MMP-13 and β-catenin in the chondrocytes.
Objective To investigate the effects of xianl inggubao (XLGB) on subchondral bone and articular cartilage in the rat osteoarthritis model induced by anterior cruciate l igament transection (ACLT). Methods Twentyfour 3-month-old female SD rats were divided randomly into 3 groups (n=8): Sham group (group A), ACLT group (group B) and XLGB group (group C). The osteoarthritis model was made by ACLT in groups B and C, the joint cave was sutured after exposure of ACL in group A. After 4 days, XLGB was given at 250 mg/(kg·d) in group C and the equivalent amount of sal ine was given in groups A and B. After 12 weeks, the gross appearance of femoral condyles was observed, the degree of cartilagedegeneration was scored by Mankin scoring system. The immunostaining for MMP-13 was performed to investigate the effect of XLGB on prevention of cartilage matrix loss. The bone mineral density (BMD) measurement and bone histomorphometric analysis were done in subchondral bone of right distal femur and proximal tibia after 12 weeks. Results The gross appearance of femoral condyles showed that ulcer in the group C was smaller than that in group B after 12 weeks. The Mankin’s scale and IA value for MMP-13 in group C were markedly lower than those in group B (P lt; 0.05). BMD of the subchondral bone in the group B was significantly lower than those in the groups A and C (P lt; 0.05). The bone mass in group C were significantly higher than that in group B (P lt; 0.05). Conclusion Oral administration of XLGB (250 mg/ kg per day) for 12 weeks could prevent the cartilage degeneration of rats after ACLT, down-regulating MMP-13 and increasing subchondral bone mass might participate in this process.
To evaluate the effects of XiangLingGuBao (XLGB) on femoral fracture heal ing in ovariectomized (OVX) rats. Methods Forty 12-week-old female SD rats weighing (258 ± 14) g were divided randomly into 4 groups (n=10 per group): group A, sham operation by opening the abdominal cavity; group B, bilateral ovariectomy; group C, bilateral ovariectomy, transverse midshaft fracture of the right femur with intramedullary nail fixation, and normal sal ine by gavage; group D, bilateral ovariectomy, transverse midshaft fracture of the right femur with intramedullary nail fixation, and 250 mg/(kg•d) XLGB by gavage. The weight of rabbits in groups A and B was measured 0, 1, 2, 3, 4 and 5 weeks after operation. The right femur of each rat was obtained 5 weeks after operation. Total femur bone mineral density (tBMD), distal femur bone mineral density (dBMD) and middle femur bone mineral density (mBMD) were measured by double energy X-ray absorptiometry CR filming, HE staining and immunohistochemistry staining of groups C and D were performed. Results The weight of rats in group B was obviously higher than that of group A at 3, 4 and 5 weeks after operation (P lt; 0.05), indicating the animal model of postmenopausal osteoporosis was establ ished successfully. CR films showed more callus and obscure fracture l ine in group D, while less callus and distinct fracture l ine in group C. The tBMD and the dBMD of group B were far less than that of group A, the mBMD of group D was significantly higher than that of group C(P lt; 0.05), the tBMD and the dBMD of group D were higher than that of group C, but no significant difference was evidentbetween two groups (P gt; 0.05). Histology observation showed, when compared with group C, most fracture ends in groupD reached bone union, and the introduction of capillaries was evident in the marrow cavity. Immunohistochemistry staining demonstrated that the BMP-2 integrated absorbance (IA) value in groups C and D was 2.236 6 ± 0.181 8 and 3.727 3 ± 0.874 2, respectively, the VEGF IA value in groups C and D was 2.835 5 ± 0.537 0 and 3.839 6 ± 0.223 0, respectively, indicating there were significant differences between two groups (P lt; 0.05). Conclusion XLGB can obviously promote the femoral fracture heal ing in OVX rats, and speed the transformation of woven bone into lamellar bone, which may rely on its role of enhancing expression of BMP-2 and VEGF.