Farnum C E, Wilsman N J
Department of Anatomy, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Calcif Tissue Int. 1993 Feb;52(2):110-9. doi: 10.1007/BF00308319.
Postnatal bone growth occurs by the process of endochondral ossification in cartilaginous growth plates at the ends of long bones. The rate and extent of long bone growth is determined by a combination of chondrocytic proliferation, matrix production, and increase in chondrocytic height in the direction of growth during cellular enlargement. In this study, single pulse and/or repeated pulse labeling with the thymidine analog bromodeoxyuridine (BrdU) was used to study the role of cellular proliferation in controlling long bone growth. Variables studied included progression of the label over time following a pulse, and patterns and progression of the label over time following repeated pulse labeling for 24 and 48 hours. Examination was made of the proliferative characteristics of chondrocytes, the spatial pattern of cellular proliferation, and cell cycle kinetics. With respect to the spatial pattern of proliferative chondrocytes, results suggest that chondrocytes within a column are more synchronized with each other than are chondrocytes in different columns. This is consistent with the concept that each column represents a clonal expansion of a stem cell, which may proceed independently from adjacent columns. Despite this apparent heterogeneity, all chondrocytes in the proliferative zone complete at least one cell cycle in 24-28 hours. This estimate of the cell cycle time is significantly shorter than previous estimates of cell cycle times in similar growth plates. Our results also suggest that chondrocytes entering the cell cycle in the proximal part of the growth plate spend an average of 4 days in the proliferative cell zone, representing approximately four cellular divisions. After leaving the cell cycle, an additional 48 hours is required for the label to reach the terminal chondrocyte, which represents the time required to complete hypertrophy. These data are important when considering hypotheses concerning both the role of controls on proliferation in the determination of overall rate of long bone growth, as well as the interplay between proliferation and hypertrophy in regulating the overall amount of growth achieved by a given growth plate.
出生后骨骼生长通过长骨末端软骨生长板中的软骨内成骨过程发生。长骨生长的速度和程度由软骨细胞增殖、基质产生以及细胞增大期间在生长方向上软骨细胞高度增加共同决定。在本研究中，使用胸腺嘧啶类似物溴脱氧尿苷（BrdU）进行单脉冲和/或重复脉冲标记，以研究细胞增殖在控制长骨生长中的作用。研究的变量包括脉冲后标记随时间的进展，以及重复脉冲标记24小时和48小时后标记随时间的模式和进展。对软骨细胞的增殖特性、细胞增殖的空间模式和细胞周期动力学进行了检查。关于增殖性软骨细胞的空间模式，结果表明同一柱内的软骨细胞彼此之间比不同柱内的软骨细胞更同步。这与每个柱代表一个干细胞的克隆扩增的概念一致，该克隆扩增可能独立于相邻柱进行。尽管存在这种明显的异质性，但增殖区内的所有软骨细胞在24 - 28小时内至少完成一个细胞周期。这个细胞周期时间的估计值明显短于先前对类似生长板中细胞周期时间的估计。我们的结果还表明，在生长板近端进入细胞周期的软骨细胞在增殖细胞区平均花费4天，代表大约四次细胞分裂。离开细胞周期后，标记物到达终末软骨细胞还需要额外48小时，这代表完成肥大所需的时间。在考虑关于控制增殖在确定长骨总体生长速率中的作用以及增殖与肥大在调节给定生长板实现的总体生长量中的相互作用的假设时，这些数据很重要。
