Current and future uses of skeletal stem cells for bone regeneration

The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.     

Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

Bone marrow-derived mesenchymal stem cells(BMSCs) play a critical role in the osseointegration of bone and orthopedic implant. However, osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium's inherent defects. Surface modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell fate. Here, we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its alloys. We will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration, and discuss recent advances in understanding their role in regenerative medicine. We aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.     

Effects of manganese-supplemented diets on growth performance,blood biochemistry,nitrogen metabolism and skeletal development of rex rabbits

(Background) Manganese (Mn) is an essential mineral, although its effects on rabbits is not clear. (Research Purpose) This study was conducted to investigate the effects of the level of supplementation of dietary manganese on growth performance, blood biochemistry, nitrogen metabolism and skeletal development of growing Rex rabbits. (Methods) Two hundred 3-month-old healthy Rex rabbits with similar body weights were randomly divided into 5 groups (A, B, C, D, E), with 40 replicates in each group. The rabbits in the 5 groups were fed a basal diet containing 0, 5, 10, 20 and 40 mg/kg manganese (in the form of manganese sulfate), respectively. The trial included 7 days for adaptation and 29 days of testing. Seven days before the end of feeding, eight rabbits from each group were transferred into a metabolic cage for metabolic testing. (Results) The results showed that supplemental dietary manganese levels did not significantly influence final body weight (FBW) or average daily feed intake (ADFI) (P＞0.05). Average daily gains (ADG) were significantly higher in the 20 mg/kg manganese group than in the other groups, and the ratio of feed to body weight gain (F/G) was significantly affected by manganese level (P < 0.05). No significant differences were found in the digestion coefficients among the groups (P > 0.05). Regarding carcass traits, the thymus index and total fat were significantly different (P < 0.05) among the groups, but there were no other significant differences (P > 0.05). The addition of manganese had no significant effect on the intake of nitrogen (IN), fecal nitrogen (FN), digestible nitrogen (DN) or the apparent digestibility of nitrogen (NAD). Compared to the other groups, urinary nitrogen (UN) was lower in the 20 mg/kg group, although nitrogen deposition (RN), nitrogen utilization (NUR) and the biological potency of nitrogen (NBV) were higher in this group (P < 0.05). As the amount of manganese added to the diet increased, serum triglycerides decreased (P < 0.05). Serum Mn-SOD was significantly lower in the 5 mg/kg manganese group than in the other groups (P < 0.05). The results of this study demonstrate that a diet with supplemented manganese can improve Rex rabbit growth performance and increase RN, NUR and NBV. There were no significant effects of different dietary levels of Mn on the ratio of bone to meat (P > 0.05) or bone strength (P < 0.05). (Conclusion) In conclusion, we determined that the optimal level of manganese supplementation in the diet of growing Rex rabbits was 20 mg/kg, which was also found to reduce nitrogen emissions into the environment.     

Polycystin-1 may play an important role in mechanical modulation of bone growth and healing

Mechanical stress is known to modulate bone growth and healing. However, the mechanisms underlying the mechanotransduction are not fully understood. Previous studies show that PC1 is a promising candidate among proteins that may play a role in the mechanotransduction process as it has been shown to function as a flow sensor in renal epithelium and it is known to be important for the growth of for skeletal development. We hypothesized that PC1 plays an important role in bone responses to mechanical stress. PC1 is required for the proliferation, differentiation and survival of periosteal osteochondroprogenitor cells upon mechanical stimulation of bone. Using both genetically manipulated animal models and animals undergoing are necessary to test this hypothesis.     

钙、磷摄入对骨代谢及骨组织形态影响的研究进展

骨代谢始终贯穿于动物的生命过程之中,而机体摄入的钙、磷水平和钙、磷比例又是骨代谢的重要影响因素。钙、磷摄入水平和比例的改变会使甲状旁腺激素（PTH）、降钙素（CT）和1α,25-双羟维生素D3[1,25-（OH）2D3]的水平产生变化,影响RANK／RANKL／OPG系统对骨细胞功能的调控,进而对骨代谢及骨组织形态产生影响。骨唾液酸蛋白（Bone Sialoprotein,BSP）是目前评价成骨细胞分化和骨骼矿化情况的新指标,研究BSP表达水平的变化规律,可以从分子水平解释钙、磷摄入水平和比例对骨组织形态影响的机理。而骨组织形态计量学（Bone Histomorphometry）则是研究钙、磷摄入水平和比例对骨组织形态影响的重要方法。     

The expense for one implantation of a banked bone allograft from a cadaveric donor and the issues affecting current advanced medical treatment in the Japanese orthopaedic field

Demand for banked bone allografts is increasing in Japan; however, there are too few bone banks and the bone bank network is not well-established. One reason for this was lack of funding for banks. Bone banks had to bear all material expenses of banked bone allografts themselves because this was not designated a covered expense. In December 2004, the Japanese government started a new “Advanced Medical Treatment” administration system which allowed an approved institution to charge the expense of authorized advanced medical treatments directly to patients. The treatment named “Cryopreserved allogenic bone and ligamentous tissue retrieved from cadaveric donor” was approved as an advanced medical treatment in March 2007. We present the calculation method and the expense per implantation of a banked bone allograft from a cadaveric donor under this treatment and raise issues which affect this advanced medical treatment and remain to be resolved in the Japanese orthopaedic field.     

Rat bone marrow derived mesenchymal progenitor cells support mouse ES cell growth and germ-like cell differentiation

Mouse embryonic fibroblasts (MEFs) have been used as feeder cells to support the growth of mouse embryonic stem cell (mESC) and primordial germ cells (PGC) in culture for many years. However, MEF preparation is a complex and tedious task. Recently, there are reports indicating that the microenvironment provided by bone marrow stromal cells could support the survival of embryonic-like stem cells in bone marrow. In this report, rat bone marrow derived mesenchymal progenitor cells (MPC) were used as feeder cells to culture mouse Oct4-GFP ES cell and ES cell derived germ cells. FACS results show that similar to MEF, rat MPC could efficiently support growth of the mouse Oct4-GFP ES cell line in culture (MPC 85.5 ± 5.1% vs MEF 84.1 ± 6.2%). ES cells could be subcultured for >15 passages without losing morphological characteristics. The cultured cells expressed stem cell marker alkaline phosphatase, Oct4, Sox2, and SSEA-1. Furthermore, rat MPC cells were able to support survival of germ cells isolated from mouse Oct4-GFP ES cell formed embryoid bodies (EB). After induction by retinoic acid for 7 days, some isolated cells differentiated to spermatogonial stem-like cells, expressing Mvh, Stra-8, Hsp90-α, integrinβ1 and α6. Compared with traditional MEF culture systems, the rat MPC culture system is effective in supporting ES cell growth and is easy to prepare.