Fig. 2.

Lin28a overexpression decreases proliferation and increases cell death in chondrocytes. (A) Growth of Col2-Cre:Lin28a^c mice (black squares), assessed by body weight, is mildly impaired compared with that of Cre-negative Ctrl (open circles) (n = 5; *P < 0.05 vs. Ctrl). Error bars depict mean ± SEM. (B) Growth plate morphology of the proximal tibia of postnatal 4.5-d-old mice. Col2-Cre:Lin28a^c mice with one allele (heterozygote) and two alleles (homozygote) of the Lin28a^c transgene are indicated by Lin28a (Tg) and Lin28a (Tg/Tg), respectively. (Lower) Cell density of the growth plate is decreased in the columnar proliferating zone of Lin28a transgenic mice. Transgenic mice show a somewhat disorganized columnar structure with the appearance of enlarged “hypertrophic-like” chondrocytes. (Original magnification, Top, ×40; Bottom, ×200.) (C) BrdU labeling index is reduced in postnatal 4.5-d-old heterozygous (Tg) and homozygous (Tg/Tg) Lin28a transgenic mice. (Magnification, ×40.) (D) Number of TUNEL-positive cells was increased in the growth plate of the transgenic tibia of postnatal 2.5-d-old Lin28a mice. Cell death was not rescued by simultaneous ablation of Trp53 (Col2-Cre:Lin28a^c:TrP53^fl/fl, labeled as Lin28a:Trp53). (Magnification, ×40.) (E) Quantification of the BrdU labeling index (n = 3; *P < 0.05 vs. Ctrl; **P < 0.05 vs. Tg). (F) Quantification of TUNEL-positive cells (*P < 0.05 vs. Ctrl). There is no significant difference between Lin28a transgenic mice and Lin28a:Trp53 doubly mutant mice.