利用者:加藤勝憲/軟骨内骨化

加藤勝憲/軟骨内骨化
Light micrograph of undecalcified epiphyseal plate showing endochondral ossification: healthy chondrocytes (top) become degenerating ones (bottom), characteristically displaying a calcified extracellular matrix.
解剖学用語 [ウィキデータを表示]

軟骨内骨化[1][2]は、哺乳類の骨格系の胎児期の発達において、骨組織が産生される2つの重要な過程のうちの1つである。骨組織が産生されるもう一つの過程である膜内骨化とは異なり、軟骨内骨化では軟骨が存在する。軟骨内骨化はまた、長骨の初歩的形成[3]、長骨の長さの成長[4]、骨折の自然治癒[5]に不可欠な過程である。

Endochondral ossification is one of the two essential processes during fetal development of the mammalian skeletal system by which bone tissue is produced. Unlike intramembranous ossification, the other process by which bone tissue is produced, cartilage is present during endochondral ossification. Endochondral ossification is also an essential process during the rudimentary formation of long bones, the growth of the length of long bones, and the natural healing of bone fractures.

Growth of the cartilage model

軟骨モデルは、軟骨細胞の継続的な細胞分裂によって長さを増し、それに伴って細胞外マトリックスがさらに分泌される。これは間質成長と呼ばれる。軟骨モデルは、軟骨周囲層から発生する新しい軟骨芽細胞を伴って、軟骨外表面の細胞外マトリックスがさらに追加されることにより、厚みも成長する。

The cartilage model will grow in length by continuous cell division of chondrocytes, which is accompanied by further secretion of extracellular matrix. This is called interstitial growth. The process of appositional growth occurs when the cartilage model also grows in thickness due to the addition of more extracellular matrix on the peripheral cartilage surface, which is accompanied by new chondroblasts that develop from the perichondrium.

Primary center of ossification

The first site of ossification occurs in the primary center of ossification, which is in the middle of diaphysis (shaft). Then:

1. Formation of periosteum

   The perichondrium becomes the periosteum. The periosteum contains a layer of undifferentiated cells (osteoprogenitor cells) which later become osteoblasts.

2. Formation of bone collar

   The osteoblasts secrete osteoid against the shaft of the cartilage model (Appositional Growth). This serves as support for the new bone.

3. Calcification of matrix

   Chondrocytes in the primary center of ossification begin to grow (hypertrophy). They stop secreting collagen and other proteoglycans and begin secreting alkaline phosphatase, an enzyme essential for mineral deposition. Then calcification of the matrix occurs and osteoprogenitor cells that entered the cavity via the periosteal bud, use the calcified matrix as a scaffold and begin to secrete osteoid, which forms the bone trabecula. Osteoclasts, formed from macrophages, break down spongy bone to form the medullary (bone marrow) cavity.

Secondary center of ossification

哺乳類では出生とほぼ同時に、長骨の両端（骨端）に二次骨化中心が出現する。骨膜芽が間充織と血管を運び込み、その過程は一次骨化センターで起こるのと同様である。一次骨化中心と二次骨化中心の間の軟骨は骨端板と呼ばれ、新しい軟骨を形成し続け、それが骨に置き換わる過程で骨の長さが長くなる。骨端板の軟骨が骨に置き換わるまで、あるいは20歳くらいまで成長は続く。一次骨化中心と二次骨化中心の結合点は骨端線と呼ばれる。

About the time of birth in mammals, a secondary ossification center appears in each end (epiphysis) of long bones. Periosteal buds carry mesenchyme and blood vessels in and the process is similar to that occurring in a primary ossification center. The cartilage between the primary and secondary ossification centers is called the epiphyseal plate, and it continues to form new cartilage, which is replaced by bone, a process that results in an increase in length of the bone. Growth continues until the individual is about 20 years old or until the cartilage in the plate is replaced by bone. The point of union of the primary and secondary ossification centers is called the epiphyseal line.

Appositional bone growth

骨幹部周辺の骨の直径の拡大は、骨膜の下に骨が沈着することによって起こる。内部空洞の破骨細胞は、究極の厚さに達するまで骨を吸収し続け、その時点では、外側からの形成と内側からの分解の速度は一定である。

The growth in diameter of bones around the diaphysis occurs by deposition of bone beneath the periosteum. Osteoclasts in the interior cavity continue to resorb bone until its ultimate thickness is achieved, at which point the rate of formation on the outside and degradation from the inside is constant.

Histology

Drawing of part of a longitudinal section of the developing femur of a rabbit. a. Flattened cartilage cells. b. Enlarged cartilage cells. c, d. Newly formed bone. e. Osteoblasts. f. Giant cells or osteoclasts. g, h. Shrunken cartilage cells. (From “Atlas of Histology,” Klein and Noble Smith.)

軟骨内骨化では、ライトマイクロスコープレベルで5つの異なるゾーンが見られる。

Name	Definition
Zone of resting cartilage	This zone contains normal, resting hyaline cartilage.
Zone of proliferation / cell columns	In this zone, chondrocytes undergo rapid mitosis, forming distinctive looking stacks.
Zone of maturation / hypertrophy	In this zone, the chondrocytes undergo hypertrophy (become enlarged). Chondrocytes contain large amounts of glycogen and begin to secrete alkaline phosphatase.
Zone of calcification	In this zone, chondrocytes are either dying or dead, leaving cavities that will later become invaded by bone-forming cells. Chondrocytes here die when they can no longer receive nutrients or eliminate wastes via diffusion. This is because the calcified matrix is much less hydrated than hyaline cartilage.
Zone of ossification	Osteoprogenitor cells invade the area and differentiate into osteoblasts, which elaborate matrix that becomes calcified on the surface of calcified cartilage. This is followed by resorption of the calcified cartilage/calcified bone complex.

Fracture healing

骨折治癒の過程で軟骨が形成されることが多く、これをカルスと呼ぶ。この軟骨は、軟骨内骨化という過程を経て、最終的に新しい骨組織に成長する。最近、アパタイトのような生体模倣骨は、細胞外カルシウム感知受容体（CaSR）の過剰刺激を通じて、軟骨内骨化経路を通じた骨の形成を阻害することが示された[6]。

During fracture healing, cartilage is often formed and is called callus. This cartilage ultimately develops into new bone tissue through the process of endochondral ossification. Recently it has been shown that biomimetic bone like apatite inhibits formation of bone through endochondral ossification pathway via hyperstimulation of extracellular calcium sensing receptor (CaSR).

Examples in human body

管状骨と扁平骨、脊椎骨、頭蓋底、篩骨、鎖骨の端は、軟骨内骨化によって形成される[7]。

Tubular and flat bones, vertebrae, the skull base, ethmoids, and the ends of the clavicles are formed by endochondral ossification.

See also

• Intramembranous ossification
• Ossification

References

[[Category:骨]]