Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio, USA.
Department of Anatomy and Neurobiology, Musculoskeletal Research Group, Northeast Ohio Medical University, Rootstown, Ohio, USA.
J Exp Zool B Mol Dev Evol. 2020 Sep;334(6):339-349. doi: 10.1002/jez.b.22990. Epub 2020 Jul 29.
Bowhead whales are among the longest-lived mammals with an extreme lifespan of about 211 years. During the first 25 years of their lives, rib bones increase in mineral density and the medulla transitions from compact to trabecular bone. Molecular drivers associated with these phenotypic changes in bone remain unknown. This study assessed expression levels of osteogenic genes from samples of rib bones of bowheads. Samples were harvested from prenatal to 86-year-old whales, representing the first third of the bowhead lifespan. Fetal to 2-year-old bowheads showed expression levels consistent with the rapid deposition of the bone extracellular matrix. Sexually mature animals showed expression levels associated with low rates of osteogenesis and increased osteoclastogenesis. After the first 25 years of life, declines in osteogenesis corresponded with increased expression of EZH2, an epigenetic regulator of osteogenesis. These findings suggest EZH2 may be at least one epigenetic modifier that contributes to the age-related changes in the rib bone phenotype along with the transition from compact to trabecular bone. Ancient cetaceans and their fossil relatives also display these phenotypes, suggesting EZH2 may have shaped the skeleton of whales in evolutionary history.
弓头鲸是寿命最长的哺乳动物之一,其极端寿命约为 211 年。在它们生命的前 25 年,肋骨的矿物质密度增加,骨髓从致密骨向小梁骨转变。与骨骼表型变化相关的分子驱动因素仍不清楚。本研究评估了取自弓头鲸肋骨样本的成骨基因的表达水平。样本取自产前至 86 岁的鲸鱼,代表了弓头鲸寿命的前三分之一。从胎儿到 2 岁的弓头鲸表现出的表达水平与骨细胞外基质的快速沉积一致。性成熟的动物表现出与低骨生成率和增加的破骨细胞生成相关的表达水平。在 25 年的生命之后,骨生成的下降与 EZH2 的表达增加相对应,EZH2 是骨生成的表观遗传调节剂。这些发现表明,EZH2 可能是至少一种表观遗传修饰因子,除了从致密骨向小梁骨的转变外,还导致了肋骨表型的年龄相关变化。古老的鲸类及其化石亲属也表现出这些表型,这表明 EZH2 可能在进化历史上塑造了鲸类的骨骼。