摘要
发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是小儿骨科最常见的疾病之一。DDH发病因素复杂,对其发生与发展的分子调控机制目前尚不清楚。了解髋关节发育过程的分子调节机制与形态学变化,对DDH发病机制的探究、早期筛查与诊疗策略的制订具有重要意义。近年来,随着发育生物学、分子生物学、基础医学以及临床医学的发展,对DDH发生、发展的风险因素以及潜在的致病机制有了更新的认知。本文综述了目前在髋关节进化过程、人类髋关节发育过程中解剖结构的变化、参与骨发育中软骨内成骨的基因及信号通路等方面的研究进展;分析了可能发生发育不稳定的时间节点,并对DDH发病的危险因素、临床筛查以及诊疗现状进行了总结。胚胎发育过程中股骨头和髋臼的相互作用决定了髋关节的形态发生,在怀孕5~12周开始出现髋关节软骨雏形,之后经历初级和次级骨化过程,发育形成具有完整结构的髋关节。调节骨发育中成软骨和成骨过程的SOX9和RUNX2等因子受到HIF、WNT、FGF及PTHRP等一系列信号通路的调控作用介导髋关节的发育进程。通过临床DDH病例基因检测(全基因组测序及全外显子测序等)发现28个左右潜在的DDH致病基因,对揭示DDH发生的分子机制具有重要意义。最后,本文还探讨了DDH研究与治疗仍面临的挑战与未来可能需要重点关注的发展方向,以期为DDH发生机制的探讨与临床诊疗策略的制订提供新的思路。
Developmental dysplasia of the hip(DDH)is one of the most common orthopaedic diseases in children.Due to the complexity of risk factors,the molecular regulatory mechanism of its occurrence and development is still not clear.Understanding the molecular regulatory mechanism and morphological changes of DDH is of great significance for the exploration of the mechanism,the formulation of early screening,diagnosis and treatment strategies.Recently,with the development of development biology,molecular biology,preclinical medicine and clinical medicine,the risk factors and potential mechanism of DDH have been investigated deeply.Here,we reviewed the formation of anatomical structure during hip joint development,genes expression and signal pathways involved in endochondral ossification.Further,we analyzed the possible development stages,which might lead to the developmental instability.Previous studies have shown that the interaction between the femoral head and the acetabulum in the embryonic development of the hip joint determines the morphogenesis of the hip joint.The embryonic cartilage of the hip joint begins to develop at 5 to 12 weeks after fertilization,followed by the development of the primary and secondary ossification processes to form the hip joint with a complete structure.Transcription factors of SOX9 and RUNX2,which regulate chondrogenesis and osteogenesis during bone development,are mediated by HIF,WNT,FGF and PTHRP signal pathways.In addition,there are 28 potential pathogenic genes of DDH identified by clinical DDH case gene detection techniques,including whole genome sequencing and whole exon sequencing,which are of great significance for revealing the molecular mechanism of DDH occurrence.In addition,we summarized the current clinical screening methods,risk factors,diagnosis and treatment of DDH.Finally,we discussed the remaining challenges and possible future directions for DDH research and interventions,which may provide new ideas for the mechanism research,and clinical diagnosis and treatment strat
作者
季策
李长伟
邓廉夫
Ji Ce;Li Changwei;Deng Lianfu(Department of Orthopaedics,Shanghai Institute of Traumatology and Orthopedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2022年第1期54-64,共11页
Chinese Journal of Orthopaedics
基金
国家自然科学基金(81972134)
上海市科委实验动物专项(19140900300)。
