Ossification (bone formation), remodelling http://www.sandgrains.com/Body-Gallery-Close-Bone-Formation.html Mark Kozsurek, M.D., Ph.D. assistant professor mark@kozsurek.hu EM I., 10/10/2018

Cells of the bony tissue Osteons are only found in the compact bone! Periosteum contains mesenchymal cells!

1. Osteocyte: The most common cell type in mature bone 1. Osteocyte: The most common cell type in mature bone. Rest in the lacunae of the bone. Adjacent osteocytes are interconnected by delicate processes. They arise from osteoblast, in fact they are the inactive forms of them.

2. Osteoblast: Differentiate from mesenchymal stem cells and are charachteristic for developing and regenerating bones as they are active and synthesize the organic components of the bony tissue called osteoid. Later they also contribute to mineralization and hydroxyapatite deposition. As they are synthesizing cells have an extended rER with ribosomes and due to these are basophylic. Mesenchymal stem cells in culture

3. Osteoclast: Osteoclasts are generated by the fusion of several macrophages and are crucial in the resorption of the bony tissue.

Bone formation Secondary ossifications Primary angiogenic ossification of Krompecher: bone is synthesized de novo by osteoblasts differentiated from mesenchymal cells found in the adventitia of small vessels – it is common during remodelling of the bone. Secondary ossifications Bone replaces a former tissue type: Intramembranous ossification: osteoblasts differentiate from mesenchymal cells and replace the preexisting connective tissue. Some bones of the skull (e.g. the calvary) and the clavicle develops by this type of bone formation. Endochondral ossification: first the hyaline cartilage is eroded, removed then replaced by osteoid producing osteoblasts. The whole process is better seen in tubular bones, but below the clavicle all the bones of the human body form this way.

A) Intramembranous ossification

Within a poorly differentiated connective tissue some mesenchymal cells transform into osteoblasts and form ossification centres. Osteoblasts synthesize and release osteoid, the organic component of the bone which calcifies soon. Trapped osteoblasts turn into inactive osteocytes. On the free surfaces of bony trabeculae new osteoblasts derived from surrounding mesenchymal cells accumulate. Following deposition of new osteoid they become trapped inactive osteocytes. And the cycle goes on… Bone is formed in a random manner first resulting in an irregular network (woven bone). Condensation of the vascularized mesenchyme on the surface of the developing bone gives the periosteum. Under the periosteum woven bone is replaced by mature lamellar bone (Haversian system) and compact plates are created. Inside the irregular trabeculae persist and the higly vascularized tissue filling the cavities of the spongy bone diffenetiate into red bone marrow.

B M M M B OCL B M OCL OB OC Developing calvary. Bony trabeculae (B) enclose inactive osteocytes (OC) and possess osteoid-synthesizing osteoblasts (OB) mainly on their external surface and osteoclasts (OCL) on the opposite sides. Osteoblast differentiate from mesenchymal cells. Osteoclasts are generated by the fusion of several macrophages and are crucial in the resorption of the boney tissue.

OB B OC OCL OCL M

B) Endochondral ossification Apoptotic chondrocytes are removed by chondroclasts and osteoblasts differentiating from mesenchymal cells sattle down on the surfaces of preserved mineralized inerterritorial matrix of cartilage.

zone of resting cartilage zone of proliferation 1. 2. EPIPHYSEAL PLATE: zone of resting cartilage zone of proliferation zone of degenaration and matrix calcification zone of mesenchymal invasion 3. 4.

During the fetal period the hyalin cartilage model of the tubular bones appear. Perichondrium has mesenchymal cells some of which differentiate into osteoblasts, thus, the perichondrium is slowly replaced by periosteum. Periosteum and increasing number of osteoblasts arising from that form a bony sheath which is against the diffusion of nutrients and oxygen: hyaline cartilage degenerates and the interteritorial matrix calcifies. Apoptotic chondrocytes are removed and osteoblasts aggregate on the surfaces of trabeculae constituted by the persisting mineralized matrix. Osteoid sythesis begins and primary ossification centers develop still in the fetal period. Due to the invasion of small vessels into the epiphyseal cartilages and appearance of mesenchymal cells differentiating into bone-producing osteoblasts secondary ossification centers appear during childhood. Primary and secondary ossification centers are getting isolated by the epiphyseal cartilage/plate. This disk-like structure with its proliferatating chondrocytes is the source of longitudinal growth of these bones. Longitudinal growth is only possible while epiphyseal plates are present. They will slowly disappear by puberty due to the increasing concentration of sexual hormons.

Secondary ossification centers, epiphyseal plates 4 ½ years 11 years adult

zone of degeneration and matrix calcification zone of proliferation zone of degeneration and matrix calcification (swollen cells with pycnotic nuclei, darker interterritorial substance)

zone of degeneration and matrix calcification chondroclast zone of degeneration and matrix calcification red bone marrow

bony trabecula (spicule) osteocytes inside, osteoblasts on its surface bony trabecula (spicule)

Bone remodelling A lifelong process where mature bone is resorbed and a new bone is synthesized. Remodelling might also be considered as an adaptation to changing demands of mechanical loadings. In the first year of life, almost 100% of the skeleton is replaced. In adults, remodeling proceeds at about 10% per year. 1. On the surface of the trabeculae of the spongy bone Blood vessels are important as they are the sources of monocytes differentiating into osteoclasts.

2. In the Haversian systems of the compact bone mesenchymal cells Osteoclasts (from the monocyte-macrophage system) distroy concentrically arranged bony lamellae of the osteon and the resorption cavity is formed. Mesenchymal cells of the adventitia of small vessels differentiate into osteoprogenitor cells and osteoblasts which bild a new Haversian system.

blood vessel mesenchymal cells osteoblasts osteoclasts osteocytes in the old bone

puberty osteoblast osteoclast activity approx. 30-35 years

Hormonal control of bone metabolism plus: growth hormone, sexual steroids, thyroxin, vitamin-D, etc.

Osteoporosis

Uncontrolled bone resorption and synthesis resulting irregularities. Paget’s disease Uncontrolled bone resorption and synthesis resulting irregularities.

Thank you for your attention!