Farley J R, Tarbaux N M, Hall S L, Linkhart T A, Baylink D J
Department of Medicine, Loma Linda University, California 92357.
Endocrinology. 1988 Jul;123(1):159-67. doi: 10.1210/endo-123-1-159.
The studies summarized in this report were intended to determine whether salmon calcitonin had direct effects on bone formation indices in vitro. The results of these investigations demonstrate acute effects of calcitonin on skeletal tissues derived from embryonic chickens to increase calvarial cell proliferation ([3H]thymidine incorporation into DNA) and bone matrix synthesis ([3H]proline incorporation into collagen, as [3H]hydroxyproline) in intact calvaria and tibiae. The effects of calcitonin on [3H]thymidine incorporation were significant at 1 mU/ml (0.08 nM; P less than 0.05), additive with respect to the action(s) of F (calcitonin increased the maximum effect of F, and F increased the effect of low dose calcitonin; P less than 0.01 for each), associated with an increase in total cell protein (r = 0.82; P less than 0.02), and inversely dependent on osteoblastic differentiation (r = -0.96; P less than 0.005). The effects of calcitonin to increase bone matrix synthesis ([3H]hydroxyproline incorporation, 139% and 155% of untreated control values for tibiae and calvaria, respectively; P less than 0.005 for each) were maximal at approximately 5 mU/ml (0.4 nM) and associated with a proportional increase in alkaline phosphatase activity in the bones (r = 0.71; P less than 0.05 for tibiae). These effects of calcitonin were not dependent on continuous exposure. [3H]Thymidine incorporation was increased in calvarial cells 16 h after a 4-h limited (inductive) exposure to calcitonin (at 3 mU/ml; P less than 0.01). [3H]Proline incorporation in embryonic chicken calvaria was also increased during 3 days of limited exposure (i.e. 4 h/day) to 10 mU/ml calcitonin (P less than 0.02). The proliferative action(s) of calcitonin was not unique to chicken osteoblastline cells. Salmon calcitonin also increased [3H]thymidine incorporation in the transformed murine calvarial cell lines MMB and MC-3T3-E1 and in primary cultures of cells prepared from newborn mouse calvaria (P less than 0.05 for each). Furthermore, these effects were observed at calcitonin doses (3-30 mU/ml) that also decreased murine bone resorption (i.e. 45Ca release from prelabeled neonatal mouse calvaria; P less than 0.01).
本报告中总结的研究旨在确定鲑鱼降钙素在体外是否对骨形成指标有直接影响。这些研究结果表明，降钙素对源自胚胎鸡的骨骼组织有急性作用，可增加完整颅骨和胫骨中颅骨细胞增殖（[³H]胸苷掺入DNA）以及骨基质合成（[³H]脯氨酸掺入胶原蛋白，以[³H]羟脯氨酸形式）。降钙素对[³H]胸苷掺入的影响在1 mU/ml（0.08 nM；P<0.05）时具有显著性，相对于F的作用具有相加性（降钙素增加了F的最大作用，而F增加了低剂量降钙素的作用；每种情况P<0.01），与总细胞蛋白增加相关（r = 0.82；P<0.02），并且与成骨细胞分化呈负相关（r = -0.96；P<0.005）。降钙素增加骨基质合成的作用（[³H]羟脯氨酸掺入，胫骨和颅骨分别为未处理对照值的139%和155%；每种情况P<0.005）在约5 mU/ml（0.4 nM）时最大，并且与骨骼中碱性磷酸酶活性的成比例增加相关（胫骨r = 0.71；P<0.05）。降钙素的这些作用不依赖于持续暴露。在对降钙素进行4小时有限（诱导性）暴露（3 mU/ml）16小时后，颅骨细胞中的[³H]胸苷掺入增加（P<0.01）。在对10 mU/ml降钙素进行3天有限暴露（即每天4小时）期间，胚胎鸡颅骨中的[³H]脯氨酸掺入也增加（P<0.02）。降钙素的增殖作用并非鸡成骨细胞系细胞所特有。鲑鱼降钙素还增加了转化的小鼠颅骨细胞系MMB和MC - 3T3 - E1以及新生小鼠颅骨制备的原代细胞培养物中的[³H]胸苷掺入（每种情况P<0.05）。此外，在降钙素剂量（3 - 30 mU/ml）下观察到这些作用，该剂量也降低了小鼠的骨吸收（即从预先标记的新生小鼠颅骨中释放⁴⁵Ca；P<0.01）。
