Bone remodeling is an ordered process of coupling of bone resorption and bone formation. Cytokines secreted by different bone cells and membrane molecules expressed by bone cells are involved in regulation of coupling of bone resorption and bone formation. To reveal the mechanism of bone coupling is of great significance in the study and diagnosis of osteoporosis and other metabolic bone diseases. In the present review, we summarize the progression of mechanisms by which cytokines and the related membrane molecules are regulating the coupling of bone resorption and bone formation.

Pancreatic islet β-cell mass is regulated by β-cell replication, nengenesis, apnptosis and cell size. β-cetl mass in diahetic patients is conspicuously less than that in normal subjects. Induction of β-cell regeneration and inhibition of β-cell apoptosis is the new target of diabetes treatment.

BACKGROUND: The main role that the osteoprotegedn (OPG) plays in bone tissues is to inhibilate the formation and the activity of osteoclast, while as for the receptor activator of nuclear factor-κB ligand (RANKL), it is to stimulate the differentiation and the activity of osteoclast. Both OPG and RANKL are important for the regulation of osteoclastic function. Recent studies have found the stimulative effects of adiponectin on the proliferation and the differentiation of osteoblast, as well as the coupling between adiponectin and bone metabolism. But effects of adiponectin on osteoclast remain unclear. OBJECTIVE: To investigate the effect of adiponectin on the expression of OPG and RANKL in osteoblast, and to further analyze its effects on the formation of osteoclast. DESIGN, TIME AND SETTING: A contrast observational experiment was conducted in the laboratory of Institute of 2008.MATERIALS: Cancellous bone in anterior superior lilac spine was obtained from adult normal by surgery for cell incubation. Clinical samples were provided by the Xiangya Hospital. METHODS: Human osteoblast was incubated with different doses of adiponcetin (0, 3, 10 and 30 mg/L) for 48 hours, after which OPG and RANKL mRNA and protein expression level was determined. In addition, adiponcetin was added into the co-culture system of osteoblast and peripheral blood monouclear cells for examing its effects on osteoclast formation. MAIN OUTCOME MEASURES: OPG and RANKL mRNA and protein expression in human osteoblast was determined using fluorescent quantitative polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA). Osteoclast was detected by antitartaric acid acid phosphatase staining. RESULTS: Adiponcetin inhibited osteoblast OPG mRNA and protein expression in a dose-dependent way (P < 0.05). Adiponcetin promoted osteoblast RANKL mRNA and protein expression in a dose-dependent way (P < 0.05). Adiponectin induced the osteoclasts formation in the co-culture system of osteoblast and peripheral blood monouclear cells. CONCLUSION: Adiponectin has the effect of inducing osteoclast formation via stimulating RANKL expression and inhibiting OPG

Objective To investigate the effect of preptin on proliferation and differentiation of human osteoblasts. Methods After human osteoblasts were incubated with 10-10, 10-9, 10-8 , 10-7 mol/L preptin for 24 h,the proliferation of osteoblasts was determined by[3H]thymidine incorporation and alkaline phosphatase (ALP)activity was assayed by spectrophotometric measurement. The phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase ( MAPK), extracellular signal-regulated kinase (ERK) 1/2 were assayed by Western blot. ERK inhibitor PD98059, p38MAPK inhibitor SB203580, and JNK inhibitor SP600125were used for investigating the signal pathway of preptin-stimulated osteoblast proliferation and differentiation.Results Preptin dose-dependently increased human proliferation of osteoblasts and ALP activity with the maximum effect at the concentration of l0-9 mol/L (both P<0.01 ). Preptin stimulated ERK phosphorylation in human osteoblasts, but not p38 MAPK and JNK phosphorylation. PD98059 blocked preptin-sitmulated human osteoblasts proliferation and ALP activity (both P<0.05 ), while SB203580 and SP600125 had no effect. Conclusions Preptin promotes the proliferation and differentiation of human osteoblasts through ERK pathway.

Objective To investigate the effect and mechnism of preptin on connect tissue growth factor (CTGF) in human osteoblasts. Methods Recombinant human preptin was used to treat primary human osteoblasts, and Western blot was used to detect CTGF protein level. Mitogen-activated protein kinase p38(p38MAPK), extracellular signal-regulated kinase (ERK1/2), c-jun N-terminal Kinase (JNK), and their phosphorylation levels were also detected by Western blot. MAPK inhibitors (PD98059, SP600125, or SB203580)were used to elucidate the mechnism of preptin induced expression of CTGF in human osteoblasts. Results Treatment of human osteoblasts with preptin caused a time and dose-dependent increase in CTGF secretion. Preptin induced activation of ERK, but not p38MAPK or JNK in human osteoblasts. Furhermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion. Conclusion Preptin induces CTGF expression in human osteoblasts by means of ERK/MAPK pathway.

This in vitro study demonstrated that taurine supplemented culture medium enhanced alkaline phosphatase (ALP) activity, osteocalcin secretion and mineralized matrix formation. Taurine induced activation of ERKI/2 and osteoblast differentiation, which was blocked by pretreatment of osteoblasts with ERKI/2 inhibitor (PD98059), suggesting taurine stimulated osteoblast differentiation via ERKI/2.

Objective To investigate the role of triggering receptor expressed on myeloid cells 1 (TREM1)in rats with neuropathic pain and its possible mechanism.Methods Forty-eight male a-dult Sprague-Dawley rats,weighing 220-300 g,were successfully placed intrathecal catheters,and then randomly divided into 4 groups (n=1 2 ):sham operation group (group S),neuropathic pain group (group CCI),TREM1 shRNA group (group RNAi)and negative lentivirus group (group Vi-rus).The neuropathic pain was induced by chronic sciatic nerve compression injury (CCI).In group RNAi,30 μl pGLVU6/RFP/Puro-shRNA (1×109IU/ml)was injected intrathecally 1 week before modeling.Group Virus was injected with 30 μl negative lentivirus,whereas group CCI and group S with equal amount of normal saline.MWT and TWL were measured 1 day before (baseline)and 1,3, 7,14 day after modeling.When behavioral test finished,the expression levels of TREM1,TLR4, MyD88,IκBαand p-NF-κB p65 in spinal cord were determined by Western blot.Whereas the mRNA expression levels of IL-1β,TNF-αand IL-6 in spinal cord were measured by RT-PCR.Results Com-pared with group S,the expression levels of TREM1 in groups CCI and Virus significantly increased (P<0.05).While compared with group CCI,the TREM1 expression of group RNAi in spinal cord significantly decreased (P<0.05).Compared with group S,MWT and TWL of groups CCI,Virus and RNAi after modeling and the expression of IκBαsignificantly decreased (P<0.05),whereas the expression of TLR4,MyD88,p-NF-κB p65 increased significantly (P<0.05),as well as the expres-sion of IL-1β,TNFαand IL-6 mRNA (P<0.05).Compared with group CCI,the MWT and TWL of group RNAi after modeling and the expression of IκBαremarkably increased (P<0.05),whereas the expression of TLR4,MyD88 and p-NF-κB p65 in the spinal cord remarkably decreased (P<0.05), as well as the expression of IL-1β,TNF-αand IL-6 mRNA (P<0.05).Conclusion TREM1 knock-down can alleviate neuropathic pain,the underlying mechanism might be the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the changes of serum C-X-C motif ligand 13 (CXCL13) concentration in senior patients undergoing total hip replacement and its role in post-operative dys-function(POCD).Methods Eighty consecutive senior patients aged 65-80 years with BMI 18.4-27.3 kg/m2,ASA physical status Ⅱ or Ⅲ,were recruited and scheduled to undergo hip joint replacement operation.Neuropsychological test was performed 1-5 d after operation and patients were divided into POCD group and non-POCD group.Serum C reactive protein (CPR),procalcitonin (PCT),IL-6, TNF-α,CXCL13 concentration were detected 1 d before and 1,2,3,4,5 d after operation. Results A total of 21 (26%)patients developed POCD 1-5 d after operation (recruited in POCD group),and the other 59 patients were recruited in non-POCD group.Compared with the time point of 1 d before operation,serum CRP,PCT,IL-6,TNF-αand CXCL13 concentration were higher 1-5 d after operation in all patients (P<0.05).The concentrationsof these factors were higher in patients from POCD group than in those from non-POCD group 1-5 d after operation (P < 0.05). Conclusion The CXCL13 concentration insenior patients undergoing total hip replacement who devel-oped POCD were higher than in those who did not developed POCD.Whether it is correlated with POCD remains further study.

Objective To evaluate the role of C-X-C motif chemokine 13 (CXCL13) in sepsis-associated encephalopathy in mice.Methods A total of 64 healthy male C57BL/6J mice,aged 3-4 months,weighing 20-25 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (Sham group),sepsis group (S group),CXCL13 siRNA group (si-CXCL13 group) and negative control siRNA group (si-control group).5-bromo-2-deoxyuridine (BrdU) 50 mg/kg was intraperitoneally injected twice a day for 3 consecutive days in the four groups,and then lipopolysaccharide 500 μg/kg was intraperitoneally injected to establish the sepsis model in S,si-CXCL13 and si-control groups.CXCL13 siRNA 5 μl and siRNA 5 μl were injected into the left lateral cerebral ventricle in si-CXCL13 and si-control groups,respectively,at 3 days before establishing the model.Morris water maze test was performed at 5 days after establishing the model.The escape latency,time spent in the target quadrant,and the number of crossing the platform were recorded.Mice were sacrificed after the end of test,brains were removed and hippocampi were isolated for examination of the pathological changes of the dentate gyrus (with a light microscope) and for determination of the expression of CXCL13,C-X-C motif chemokine receptor 5 (CXCR5) and brain-derived neurotrophic factor (BDNF),and the number of BrdU and BrdU/NeuroD positive cells (by immunofluorescence).Results Compared with sham group,the escape latency was significantly prolonged,the time spent in the target quadrant was shortened,and the number of crossing the platform was reduced on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was increased,and the number of BrdU/NeuroD positive cells in the dentate gyrus was decreased in S,siCXCL13 and si-control groups,and the expression of CXCL13 and CXCR5 was up-regulated,and the expression of BDNF was down-regulated in LPS and si-control groups (P＜0.05).Compared with S group,the escape latency was significantly shortened,the time spent in the target quadrant was prolonged,and the number of crossing the platform was increased on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was decreased,the number of BrdU/NeuroD positive cells in the dentate gyrus was increased,and the expression of CXCL13 and CXCR5 was down-regulated,and the expression of BDNF was up-regulated in si-CXCL13 group (P＜0.05),and no significant change was found in the parameters mentioned above in si-control group (P＞0.05).Conclusion CXCL13 is involved in sepsis-associated encephalopathy through regulating hippocampal neurogenesis,and the mechanism may be related to down-regulating the expression of hippocampal BDNF in mice.

Bardet-Biedl syndrome (BBS) is a rare and highly heterogeneous autosomal recessive disease caused by ciliary structure abnormality or dysfunction. Here we report a case of a 23-year-old woman who was diagnosed with BBS with a rare BBS10 gene mutation. Literature review was performed with a focus to outline treatment and management plans for patients with this rare and potentially dangerous disease.