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.

项目概要 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。 75% 的儿童颞下颌关节髁损伤无需手术即可再生 机制尚不清楚，而一些患者出现强直，导致张口受限和 面部审美缺陷。 TMJ由下颌髁突、颞骨和含有丰富组织的椎间盘组成 肌腱附件。肌腱被认为发挥着将肌肉力量传递给身体的唯一功能 稳定关节，但目前尚不清楚为什么肌腱在创伤或疾病中会发生异位骨化，并且 它是否对骨骼形成有任何直接贡献。研究其完整的生物学意义 为了研究肌腱在出生后颞下颌关节生长和扩张中的作用，进行了一系列体内实验。关键 调查结果是：颞下颌关节髁由一个完善的软骨头和一个被忽视的骨头组成 出生后生长并在一生中不断扩展； b.与肌腱相连的骨头、升支和 颞骨在矿物质模式、细胞形态和 ECM（细胞外基质）方面具有独特的特征 轮廓，与传统骨（例如骨膜形成骨，PFB）不同； c.这个新的 已鉴定的骨组织（称为肌腱形成骨，TFB）源自 Scx+（scleraxis）肌腱细胞，通过 界面，并侵入邻近的软骨或骨骼，形成超越简单附着的紧密连接 肌腱和骨骼之间； d.低磷血症加速细胞增殖和转分化 无血管肌腱到 TFB，导致颞下颌关节畸形；和 e。快速、稳健地成熟 Scx+ 肌腱细胞 当颞下颌关节受到创伤时，它们的命运就会转变为软骨和骨细胞，从而导致自我修复或强直。这些 新的发现提出了以下中心假设：肌腱细胞超出了其在关节中的传统作用 运动，负责颞下颌关节髁头、支和颞的出生后生长和扩张 骨，也是颞下颌关节创伤修复和强直发作过程中的关键角色。为了检验这个假设，两个高度 提出了相关但独立的具体目标： 1) 定义肌腱在形成骨细胞中的新作用 骨髁头和支，其细胞形态、ECM 与传统骨不同 成分和矿化； 2) 定义肌腱在 TMJ 颞骨生长过程中的新作用 成体肌腱细胞的可塑性是造成创伤引起的颞下颌关节强直的原因。完成后 拟议的工作，预计将证明：a）Scx+肌腱细胞直接有助于产后 通过细胞转分化促进颞下颌关节骨头、支和颞骨的生长和扩张 机制; b) 成体肌腱细胞通过移位参与创伤时的颞下颌关节修复和强直发作 它们的细胞命运为软骨细胞和骨细胞。这项研究的结果将在很大程度上填补这方面的知识空白 未知但重要的领域，通过提出一种新型的肌腱衍生骨来修改当前的教条，并奠定 为开发创伤和疾病中颞下颌关节恢复的新方法奠定了基础。