Novel roles of tendon during TMJ postnatal growth and onset of diseases

肌腱在颞下颌关节出生后生长和疾病发生过程中的新作用

• 批准号: 10445200
• 负责人: Yan Jing
• 金额: $ 35.98万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-11 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10445200
• 关键词: Adult; Animal Model; Ankylosis; Area; Biological; Birth; Bone Growth; Bone Spur; Bone Tissue; Buffers; Cartilage; Cell Proliferation; Cells; Cellular Morphology; Child; Chondrocytes; Complex; Defect; Degenerative Disorder; Diagnosis; Disease; Epiphysial cartilage; Esthetics; Extracellular Matrix; Extracellular Matrix Proteins; Face; Female; Foundations; Goals; Growth; Head; Heterotopic Ossification; High Prevalence; Human body; Hypophosphatemia; Ice; Injury; Invaded; Joint repair; Joints; Knowledge; Longevity; Mandibular Condyle; Minerals; Muscle; Myofascial Pain Syndromes; Names; Natural regeneration; Onset of illness; Operative Surgical Procedures; Oral cavity; Osteogenesis; Pain management; Patients; Pattern; Periosteum; Phosphorus; Physical therapy; Play; Population; Practice Management; Research; Research Proposals; Rest; Role; Series; Site; Source; TMD treatment; Temporal bone structure; Temporomandibular Joint; Temporomandibular Joint Disorders; Tendon structure; Testing; Tissues; Trauma; Work; arthropathies; base; bone; bone cell; cartilage cell; cell type; craniofacial bone; experimental study; imaging modality; in vivo; injured; insight; joint formation; joint injury; joint mobilization; mechanical force; mineralization; novel; novel strategies; postnatal; repaired; restoration; scleraxis; skeletal; skeletal disorder; transdifferentiation; treatment strategy

Project Summary The Temporomandibular joint (TMJ) is one of the most complex joints in the human body, with high prevalence of diseases and trauma. 75% of the injured TMJ condyles in children can regenerate without surgery by an unknown mechanism, whereas some patients develop ankylosis, leading to restricted mouth opening and facial aesthetic defects. TMJ is composed of the mandibular condyle, temporal bone, and a disc with abundant tendon attachments. Tendon has been thought to play the sole function of transmitting muscle forces to stabilize joints, yet it is largely unclear why tendon undergoes ectopic ossification in trauma or diseases, and whether it has any direct contribution to skeletal formation. To investigate the full biological significance of tendon in TMJ postnatal growth and expansion, a series of in vivo experiments were performed. The key findings are a. the TMJ condyle is composed of a well-established cartilage head and an overlooked bony head that grows after birth and continuously expands during lifespan; b. the tendon-attached bony head, ramus, and temporal bone share unique features in mineral pattern, cell morphology, and ECM (extracellular matrix) profiles, which are distinct from conventional bone (such as periosteum-formed bone, PFB); c. this newly identified bone tissue (named tendon-formed bone, TFB) originates from Scx+ (scleraxis) tendon cells via an interface, and invades the adjacent cartilage or bone to form a tight connection beyond a simple attachment between tendon and bone; d. Hypophosphatemia accelerates cell proliferation and transdifferentiation of the avascular tendon to TFB, resulting in a malformed TMJ; and e. mature Scx+ tendon cells rapidly and robustly switch their fate to cartilage and bone cells upon TMJ trauma, giving rise to a self-repair or ankylosis. These novel findings raise the following central hypothesis: tendon cells, beyond their conventional role in joint movement, are responsible for the postnatal growth and expansion of TMJ condyle head, ramus, and temporal bone, as well as a key player during TMJ trauma repair and ankylosis onset. To test this hypothesis, two highly related, yet independent Specific Aims are proposed: 1) To define novel roles of tendon in forming bone cells of the bony condyle head and ramus, which are distinct from conventional bone in cell morphology, ECM components, and mineralization; 2) To define novel roles of tendon during TMJ temporal bone growth, as well as the plasticity of adult tendon cells that are responsible for trauma-induced TMJ ankylosis. Upon completion of the proposed work, it is expected to demonstrate that a) Scx+ tendon cells directly contribute to the postnatal growth and expansion of TMJ bony head, ramus, and temporal bone through a cell transdifferentiation mechanism; and b) adult tendon cells participate in TMJ repair and ankylosis onset upon trauma by shifting their cell fate to chondrocytes and bone cells. Findings from this study will fill knowledge gaps in this largely unknown but vital area, revise the current dogma by raising a new type of tendon-derived bone, and lay the foundation for developing novel approaches to the restoration of TMJ in trauma and disease.

项目摘要 颞下颌关节（TMJ）是人体最复杂的关节之一，患病率很高 疾病和创伤。儿童中有75％的受伤的TMJ con可以在不手术的情况下再生 未知的机制，而一些患者患有强直性，导致口腔张开率受到限制和 面部美学缺陷。 TMJ由下颌con，颞骨和丰富的圆盘组成 肌腱附件。肌腱被认为发挥了传播肌肉力的唯一功能 稳定关节，但在很大程度上尚不清楚为什么肌腱在创伤或疾病中发生异位骨化，而 它是否对骨骼形成有任何直接贡献。研究的全部生物学意义 TMJ产后生长和膨胀中的肌腱，进行了一系列体内实验。钥匙 发现是。 TMJ Condyle由一个完善的软骨头和一个被忽视的骨头组成 这在出生后生长，并在寿命中不断扩展； b。肌腱连接的骨头，拉姆斯和 颞骨在矿物模式，细胞形态和ECM（细胞外基质）中具有独特的特征 特征，与常规骨不同（例如骨膜形成骨，PFB）； c。这个新 鉴定出的骨组织（命名为肌腱形成的骨，TFB）源自SCX+（硬化）肌腱细胞 接口，并入侵相邻的软骨或骨头以形成紧密的连接，而不是简单的附件 在肌腱和骨头之间； d。低磷酸血症加速了细胞增殖和转变 TFB的血管肌腱，导致TMJ畸形；和e。成熟的SCX+肌腱细胞快速，稳健 在TMJ创伤时，将其命运转换为软骨和骨细胞，从而引起自我修复或强直性病。这些 新发现提出了以下中心假设：肌腱细胞，超出其在关节中的常规作用 运动，负责TMJ Condyle Head，Ramus和Perimal的产后生长和扩张 在TMJ创伤修复和强直性发作期间，骨骼以及关键人物。为了检验这一假设，两个高度 提出了相关但独立的特定目的：1）定义肌腱在形成形成的骨细胞中的新作用 骨头和拉姆斯（Ramus）与细胞形态中的常规骨不同，ECM不同 组件和矿化； 2）在TMJ颞骨生长过程中定义肌腱的新作用 作为负责创伤诱导的TMJ强化病的成年肌腱细胞的可塑性。完成后 提出的工作，预计将证明a）SCX+肌腱细胞直接有助于产后 TMJ骨头，拉姆斯和颞骨的生长和扩展通过细胞转分解 机制; b）成年肌腱细胞通过转移而参与创伤后的TMJ修复和强直性发作 它们的细胞命运与软骨细胞和骨细胞。这项研究的结果将填补这一知识的空白 未知但至关重要的区域，通过提出新型肌腱衍生的骨骼来修改当前的教条，并放置 开发新型方法​​来恢复创伤和疾病中TMJ的方法。