间隙连接通讯功能对小剂量甲状旁腺激素成骨效应调控的机制

AIM: To investigate mediating and regulatory effects of osteoblastic gap junctional intercelinlar communication(GJIC) on low-dose parathyroid hormones(PTH) -stimulated bone formation activities in vitro. METHODS: Rat calvarial osteoblasts (ROBs) in cultures were divided into three groups according to the different mode of exposure. Group A: vehicle (sodium acetate, SA) -treated group; Group B: 1 × 10-8 mol/L hPTH(1 -34) intermittent exposure group; Group C: 1 × 10-8 mol/L hPTH(1 - 34) + 1 × 10-7mol/L TPA exposure group. 48 h incubation cycles in three groups were repeated for eignt times. GJIC and mineralized bone nodules formation in three groups were detected using Lucifer Yellow (LY) scrape loading dye transfer (SLDT) and mineralized nodule staining together with nodule index, respectively. RESUITS: At various measuring time points of SA × 6 h in group A, PTH × 6 hin group B, PTH×6h+1 hingroupBandPTH×6h+TPA×1 bin group C, LY( + ) cell numbers were 6. 8 ±2.5, 19.5 ±6.5, 14.0 ± 3.6 and 5.7 ± 2.4, respectively. Diffusion and transfer of LY fluorescent probe was much more noticeably discerned in group B than in group A and C( P ＜ 0.01 ) Mineralized bone nodule indices were 45.2 ± 12.5, 88.0 ± 15.3 and 38. 5 ± 17.9 in group A, B and C respectively. Bone formation activity was much better reveaied in group B than in group A and C ( P ＜ 0. 01 ),whereas no statistically significant difference of bone formation activities were found in group A compared with group C( P =0. 465) . CONCLUSION:Mediations aod regulations of the coordinating signals in ostooblastic network via GJIC essentially contribute to PTH-stimulated bone anabolism. However, disruption of GJIC not only hinders ostooblastic intercellular coordination but also frustrates PTH-induced bone formation activities in vitro. Therefore, GJIC may evidently play important roles in regulations on low-dose PTH-induced bone formation.

Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.