Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17
Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17
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DOI：
10.1073/pnas.96.3.1054
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发表时间：
1999-02-02
影响因子：
11.1
通讯作者：
TeKoppele, JM
中科院分区：
文献类型：
--
作者：
Bank, RA;Robins, SP;TeKoppele, JM
Bruck综合征以骨质疏松、关节挛缩、骨骼脆弱和身材矮小为特征。我们报道骨中I型胶原末端肽内的赖氨酸残基是欠羟基化的，导致异常交联，但三螺旋中的赖氨酸残基通常是修饰的。与骨、软骨和韧带的正常交联模式相反，胶原交联主要受组织特异性酶的调节，这些酶只对端肽赖氨酸残基羟基化，而不是对分子螺旋部分羟基化。这个新的酶家族似乎为控制胶原交联的不同途径提供了主要的调节，并解释了为什么交联模式是组织特异性的，而与遗传胶原蛋白类型无关。基因组筛选只发现了17p12染色体上的一个区域，在那里所有受影响的兄弟姐妹共享一组血统相同的单倍型；这可能是BS （Bruck综合征）位点，因此是骨端肽基赖基羟化酶所在的区域。进一步了解这种酶对端肽赖基羟化酶异常表达的情况具有重要意义，如纤维化和疤痕形成。
Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament show unaltered telopeptide hydroxylation as evidenced by normal patterns of crosslinking, The results provide compelling evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. This new family of enzymes appears to provide the primary regulation for controlling the different pathways of collagen crosslinking and explains why crosslink patterns are tissue specific and not related to a genetic collagen type. A genome screen identified only a single region on chromosome 17p12 where all affected sibs shared a cluster of haplotypes identical by descent; this might be the BS (Bruck syndrome) locus and consequently the region where bone telopeptidyl lysyl hydroxylase is located. Further knowledge of this enzyme has important implications for conditions where aberrant expression of telopeptide lysyl hydroxylase occurs, such as fibrosis and scar formation.