Research Area

Skeletal System Development

Skeletal system development overview

After 7 weeks of embryonic development, bone development begins. Intramembranous osteogenesis is generally converted from direct intima of the mesophyll. Many skulls are transformed from mesophyll to cartilage and then form ossification. First, the primary bone ring is formed, and then the blood vessels invade to form the primary ossification center, which will become the backbone and the metaphysis. The vascular tissue of the ankle is indirectly ossified to form an existing ossification center. The junction of the iliac crest and the diaphysis is called a growth plate and grows between primary and secondary ossification centers with faster lateral and longitudinal growth capabilities. The first form of cartilage is gradually replaced by ossified tissue, called cartilage osteogenesis. Endochondral ossification contains intramembranous osteogenesis due to periosteal parallelism. Similarly, intramembranous osteogenesis may also undergo growth following the evolution of the cartilage internalization bone. If the skeletal system development process can be regulated, it will provide a treatment strategy for symptoms such as skeletal dysplasia.

Skeletal system development research status

Cartilage and bone constitute the body's scaffold. Cartilage tissue and bone tissue contain a small number of cells and many solid-state interstitial cells and are constantly updated to meet the needs of the body's development and support functions. Skeletal system development is simultaneous, in the first few weeks of the embryo, after the blastocyst stage and the primary blastocyst stage, the embryonic is formed, the trunk and the outer keel forming the limb bud occur. There is a layer of loose between the ectoderm and the endoderm. The cell tissue called mesenchymal; the mesenchyme gradually differentiates into various connective tissue structures such as bone, cartilage, fascia, and muscle. The mesenchymal tissue will be the earliest part of the muscle formation. Each dense mesenchymal shape will be transformed directly or indirectly into bone. The formation and occurrence of cartilage: at the 5th week of the embryo, the mesenchymal tissue gradually enlarges, becomes denser, and differentiates into a layer of cells called pre-cartilage; then the matrix is deposited between the cells. This matrix contains fibrils. Fibrils have the unique function of cartilage. Bcause the matrix appears clear and the structure is similar, the fibrils cannot be displayed by ordinary dyeing. In the hyaline cartilage, thicker white fibers are visible and deposited in the matrix. There are two simultaneous growth modes of cartilage: inner product growth. Also known as expansion growth. That is, the cartilage grows from the inside; the growth of the cartilage refers to the continuous addition of new chondrocytes and interstitial cells from the osteogenic cells of the cartilage inner layer to the cartilage surface so that the cartilage expands from the surface to the periphery. There are two ways of bone formation: intramembranous osteogenesis and cartilage osteogenesis: intramembranous osteogenesis: intramembranous osteogenesis occurs simply, and mesenchyme undergoes calcification to form a skull, facial bone, partial clavicle, and mandible. Mesenchyme first differentiates into a blood vessel-rich embryonic connective tissue membrane, where many osteoblastic cells differentiate into ossification centers. Osteoblasts begin to secrete organic interstitial cells, forming osteoids, which then deposit on them to form bone tissue. This bone tissue is initially a primary cancellous bone, has no bone plate, and has few bone salts. It is connected to many needles that are needle-like or flaky, forming many gaps. The osteogenesis process extends from the ossification center to the periphery, and the surface mesenchyme differentiates into the periosteum. The deep osteoblasts deposit new bone on the surface of the primary cancellous bone, and the bone gradually thickens and enlarges. Endothelialization of the cartilage: After birth, the growth of the tubular bone of the limb and the formation of the special structure mainly depend on the endochondral ossification of the existing osteophytes. There are two kinds of the cartilage during the end of the bone: articular cartilage: for the growth of the epiphysis. In short bones, this is the only structure of bone growth. Eucalyptus cartilage: divided into six layers, from the epiphysis to the dry end: A. The resting layer contains immature chondrocytes and small blood vessels from the epiphysis. B. Proliferation layer: The naive proliferating chondrocytes line up in a longitudinal direction and are the most active areas of chondrocyte division. These cells are characterized by several lines of solid. Rough endoplasmic reticulum with small Golgi and elongated nuclei. The cells are flat, like a string of coins. Each chondrocyte grows a lot of axons and extends to the surrounding matrix. Due to the active division, there can be multiple chondrocytes in each cartilage sag. C. Matrix synthesis layer: It is characterized by the phosphatase necessary for the synthesis of glycogen and synthetic matrix in the cell. The cells are larger than the former. There is a layer of newly synthesized cartilage matrix between cells and cells. Contains an amorphous matrix and fibrils. The axons of the cells extend toward the stroma, and the axon ends are braided. D. Cell hypertrophy: The lacuna is larger, the fibrils are compressed together in the longitudinal direction, forming a collagen bundle, and can see periodic stripes on some collagen fibers, but rarely mineralized. Due to different tissue fixation methods, the morphology of the cells is different, or the cells are hypertrophy, contain vacuoles, irregular in shape, often in the form of spines, or rounded. Ultramicroscopic observation showed that there were few organelles in the cells, the Golgi apparatus scattered, and the mitochondria and rough endoplasmic reticulum were very dispersed. E. Temporary calcification: Most cells contain dense nuclei and irregular edges, especially near the metaphysis. The mitochondria and the cytoplasmic membrane are rich in calcium, and the mineralization of the matrix begins with the deposition of small, dispersed clusters of mineral crystals, which gradually increase and increase until the crystal blocks envelop the collagen fibers. In this way, the properties of the matrix will vary greatly and most of the moisture will be lost. Chondrocytes die due to calcification of the matrix. F. Cartilage ossification: This is a thin layer of slab adjacent to the dry smash. Capillary buds are accompanied by osteoprogenitor cells through the transverse iliac crest and into this layer. The latter differentiate into osteoblasts, which ossify the stroma, which itself is surrounded by ossified matrices and becomes bone cells and bone lacunae. The bone matrix column has the same orientation as the original cartilage matrix column and is called primary cancellous bone. Later, under the action of stress, the primary cancellous bone and cartilage column were absorbed by osteoclasts and replaced by the existing trabecular bone. Thus, the epiphyseal cartilage maintains a balanced biological process: the chondrocytes continue to proliferate, thickening the tarsal plate, and on the metaphyseal side, the chondrocytes are continuously necrotic, replaced by osteoblasts, and the matrix is continuously calcified. So that the metaphyseal bones continue to grow. Finally, due to genetic constraints, the bones stop growing and synthesize the matrix at a certain age. The osteophytes are replaced by bone tissue and can no longer be seen on X-ray films. At this time, it is called osteophyte closure. The whole body has its age of appearance and closure, called bone age.

Skeletal system development regulation

Regarding the influence factors of bone formation, the most studied is bone morphogenetic protein (BMP): Role in Bone Metabolism during normal bone metabolism, bone resorption of osteoclasts (OC) is coupled to bone formation of osteoblasts (OB), maintaining a dynamic balance and ongoing bone remodeling. Osteoporosis is caused when the bone resorption of OC is relatively enhanced, or the bone formation of OB is relatively weakened, and bone resorption is greater than bone formation leading to bone loss. In recent years, with the deepening of cell biology and molecular biology research, the role of cytokines in the process of bone metabolism has received more and more attention. Cytokines regulate the differentiation, proliferation and functional activity of OB and OC during bone metabolism and play an important role in bone remodeling through autocrine, paracrine and cell adhesion. BMP is involved in all stages of bone metabolism, and BMP-2 is one of the important bone formation factors. BMP induces differentiation of intraosseous, adventitial and bone marrow stromal cells into osteoblasts, which enhances the ability of bone regeneration, and activates or induces differentiation of mesenchymal cells around the blood vessels into cartilage and osteoblasts. Hirataet al. transfected skin fibroblasts with AdBMP-2 or AdRunx2 to observe their osteogenic activity. In vitro, skin fibroblasts infected with BMP-2 secrete the BMP-2 protein, and AdRunx2 also produces the corresponding protein; transduction of bmp-2 orrunx 2 gene can increase ALP activity, ALP mRNA expression, and osteocalcin secretion. However,in vivo experiments have shown that implantation of BMP-2 infected skin fibroblasts can induce bone formation, whereas AdRunx 2 infection does not induce osteogenesis. The effects of BMP-2, BMP-7, and BMP-2/7 on bone regeneration were confirmed by a designed bone model consisting of collagen scaffolds that can hold BMPs filled with osteoblasts. Before BMP stimulates osteoblasts, osteoblasts are cultured in a collagen scaffold for 24 h, and BMP-2, BMP-7, and BMP-2/BMP-7 are used in an amount of 10 to 100 ng/mL, which can be used after 4 days. Osteocalcin, IL-6, metalloproteinase (MMP-2, MMP-9) and protease inhibitors (TIMP-1, TIMP-2), BMP-2 and BMP-2/BMP-7 were detected to enhance bone calcium mRNA expression and protein secretion, BMP-2 and BMP-2/BMP-7 up-regulate IL-6 secretion via an IL-6 pathway. BMPs increase TIMP-1 and TIMP-2 mRNA by inhibiting MMP-2 mRNA expression. Expression and protein secretion increase the production of extracellular matrix. BMP is the only growth factor that can induce mesenchymal cells to differentiate into bone tissue and is a key regulator in the formation of bone tissue.


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