瘦素在骨与软骨代谢中的作用

肥胖对机体健康的不良影响已得到越来越多的重视,但人们在研究和防治肥胖的同时,也发现肥胖对骨骼有保护作用:肥胖者很少患有骨质疏松症,髋部骨折的发生率也较低[1]。体重或体重指数(BMI)与骨密度(BMD)的相关性已经得到公认,许多研究进一步证明体重的重要组成部分———体脂量(     

Wnt信号通路在骨稳态中的作用

人体内的骨稳态是由骨形成和骨吸收活动组成的动态平衡过程.骨稳态的失衡和功能障碍是包括骨质疏松症和骨硬化症在内的多种骨骼疾病的基础.以往研究证实Wnt、BMP、PTH/PTHrP、Notch和Hedgehog等信号通路参与调控成骨细胞/破骨细胞功能及骨稳态的平衡,其中Wnt信号通路的作用尤为关键和重要.本综述以此为切入点...     

Cleft lip rhinoplasty: the role of bone and cartilage grafts

Correction of the cleft lip nasal deformity involves repositioning of the lower lateral cartilage on the cleft side to raise the dome, lengthening the columella and bringing it toward the midline, and correcting any asymmetries of the nasal floor. Additional structural support in the form of bone or cartilage grafts is often required in order to achieve the desired projection and angularity. Our experience with these grafts in a large number of patients over the past 20 years has shown them to produce good, predictable results that are long lasting, with minimum donor site morbidity. Long-term follow-up indicates that these grafts maintain their volume and original features, resulting in satisfaction among our patients.     

Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling

Sclerosteosis and Van Buchem disease are rare, high-bone-mass disorders that have been linked to deficiency in the SOST gene, encoding sclerostin. Sclerostin belongs to the DAN family of glycoproteins, of which multiple family members have been shown to antagonize bone morphogenetic protein (BMP) and/or Wnt activity. Sclerostin is specifically expressed by osteocytes and inhibits BMP-induced osteoblast differentiation and ectopic bone formation. Sclerostin binds only weakly to BMPs and does not inhibit direct BMP-induced responses. Instead, sclerostin antagonizes canonical Wnt signaling by binding to Wnt coreceptors, low-density lipoprotein receptor-related protein 5 and 6. Several lipoprotein receptor-related protein-5 mutants that cause the high-bone-mass trait are defective in sclerostin binding. Thus, high bone mass in sclerosteosis and Van Buchem disease may result from increased Wnt signaling due to the absence of or insensitivity to sclerostin.     

AMPK信号通路对骨代谢的调节作用

最近越来越多的证据显示骨质疏松症可能与肥胖症类似,也与能量代谢紊乱相关。而腺苷酸活化蛋白激酶(AMPK)是维持细胞能量平衡以及调节多种代谢相关激素的重要分子,AMPK激活后可以开启分解代谢通路以产生更多的ATP,同时会关闭合成代谢通路以减少ATP的消耗。已知AMPK不仅能被脂肪细胞分泌的脂联素和瘦素激活,还能被抗糖尿病类药物二甲双胍和噻唑烷二酮类激活,而这些脂肪因子和药物都能影响骨代谢,同时最近的研究也表明AMPK信号通路对骨代谢有调节作用。体外激活AMPK可以影响成骨,基因敲除AMPKα或β亚基会使小鼠骨量降低,骨形成和骨吸收同时增加但伴有骨重建的负平衡,但是其中涉及的具体机制并不明确。本文就AMPK的结构和功能、在骨组织细胞中的作用、与成骨成脂分化平衡的关系作一综述,并分析AMPK通路作为骨质疏松症潜在治疗靶点的可能性。     

Cellular interactions and signaling in cartilage development

The long bones of the developing skeleton, such as those of the limb, arise from the process of endochondral ossification, where cartilage serves as the initial anlage element and is later replaced by bone. One of the earliest events of embryonic limb development is cellular condensation, whereby pre-cartilage mesenchymal cells aggregate as a result of specific cell-cell interactions, a requisite step in the chondrogenic pathway. In this review an extensive examination of historical and recent literature pertaining to limb development and mesenchymal condensation has been undertaken. Topics reviewed include limb initiation and axial induction, mesenchymal condensation and its regulation by various adhesion molecules, and regulation of chondrocyte differentiation and limb patterning. The complexity of limb development is exemplified by the involvement of multiple growth factors and morphogens such as Wnts, transforming growth factor-beta and fibroblast growth factors, as well as condensation events mediated by both cell-cell (neural cadherin and neural cell adhesion molecule) and cell-matrix adhesion (fibronectin, proteoglycans and collagens), as well as numerous intracellular signaling pathways transduced by integrins, mitogen activated protein kinases, protein kinase C, lipid metabolites and cyclic adenosine monophosphate. Furthermore, information pertaining to limb patterning and the functional importance of Hox genes and various other signaling molecules such as radical fringe, engrailed, Sox-9, and the Hedgehog family is reviewed. The exquisite three-dimensional structure of the vertebrate limb represents the culmination of these highly orchestrated and strictly regulated events. Understanding the development of cartilage should provide insights into mechanisms underlying the biology of both normal and pathologic (e.g. osteoarthritis) adult cartilage.     

A role for Notch signaling in corneal wound healing

To identify the role of the Notch signaling pathway in corneal wound healing, rat corneas receiving either epithelial or stromal wounds were placed in organ culture for up to 3 and 14 days, respectively. Localization of Notch receptors—Notch1, Notch2, and their ligands—Delta1, Jagged1 was determined by immunofluorescence. Wounds were treated with a γ‐secretase inhibitor to suppress Notch signaling or recombinant Jagged1 to enhance Notch signaling and morphological changes in the epithelium and stroma were recorded. The expressions of markers of cell proliferation (Ki67) and epithelial differentiation (cytokeratin 3) were assessed by immunohistology. Notch1 and Notch2 were localized to suprabasal epithelial cells in normal corneas. During corneal wound healing, both Notch receptors were detected in suprabasal and superficial epithelial layers. Delta1 and Jagged1 were observed throughout all corneal epithelial cell layers and occasional keratocytes of the stroma in normal and wounded corneas. γ‐secretase inhibition of Notch resulted in increased epithelial cell layers, with recombinant Jagged1 activation of Notch leading to a reduction in epithelial cell layers during corneal wound healing. Correspondingly, the activation of Notch resulted in a decreased cytokeratin 3 expression in the corneal epithelium, with no effect on cellular expression of Ki67. Notch signaling pathway suppressed corneal epithelial differentiation during corneal wound healing, but had no effect on epithelial cell proliferation.     

Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair

Literature data concerning the biology and differentiation potential of mesenchymal stem cells (MSCs) have become huge in less than 10 years, although some of these data still remain contradictory. MSCs seem to be a very promising tool for cell therapy because of their peculiar characteristics, which mimic partially those of embryonic stem cells, but with some advantages in terms of availability, expandability, transplantability, and ethical implications. We discuss here the potential use of MSCs in degenerative or inflammatory diseases involving bone, cartilage, tendon and muscle tissues, on the basis of the experimental evidence.