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Cartilage, bone and
ossification (formation of bone)
Ivan VARGAInstitute of Histology and Embryology
March 12, 2020
Histology lecture
On-line documents for histology
lectures: introductory notesDear students,
until now, it hasn´t been our custom to publish any of histology lectures in freely accessible on-line form on the website of our faculty and there has been a good reason for that. The most important elements of each one of the histology lectures are high quality schematic pictures, drawings and photomicrographs. The source of these didactic materials is commonly some internationally accetedtextbooks, however, any further spread of these materials to wider public requires a consent from the publisher/copyright owner. Therefore, the lecture you will obtain is a version with significantly reduced number of figures. The only graphic materials I have been able to use come from a textbook which I co-authored, so I have the "copyright" to share them. Only other option has been to use free-access documents from the web. It is important to point out that any figure without proper commentary loses its educational value, so for the purpose of your self-study, I must refer to other textbooks we have written for you. Please feel free to contant me via an e-mail if you have any other queries. I hope, that the epidemiological situation will allow us to continue the in-person education as soon as possible, so we can get back to "classic" lectures followed by discussion, which represent the highest form of teaching and manifestation of creativity within the university education.
Best regards, prof. RNDr. Ivan Varga, PhD. ivan.varga@fmed.uniba.skwww.fmed.uniba.sk/en/science/
Connective tissue - classification
Connective tissue proper
Cartilage
Bone
CELLS
EXTRACELLULAR MATRIX
+ blood and lymph
Cartilage and bone
Cells of develop from embryonic mesenchymal cells
The amorphous extracellular matrix / ground substance is hardened to provide:
Rigidity
Support
Attachment for tissues
Cartilage (lat. cartilago, gr. chondros)
avascular (withoutvessels) and aneural(without nerves) connective tissue
firm and flexible tissue
few cells, more than 95% of the content -extracellular matrix,
surface is covered by perichondrium (a
type of connective tissue „capsule or envelope“)
Structure of cartilage
cartilage
cells
extracellular
matrix
chondrocytes
chondroblasts(in perichondrium)
Fibers
Ground substance
collagen I.
collagen II.
elastic
Perichondrium – envelope („capsule“ of a cartilage)
Fibrous layer =
Dense connective tissue
Chondrogenic layer =
chondroblasts
Cartilage
Perichondrium(gr. peri = around, chondros
= cartilage)
Cover of connective tissue proper (dense)
Nutrition and growth
2 layers: Outer: connective tissue proper
collagen I, fibroblasts, blood vessels
Inner: more cells – chondroblasts
Blood vessels
not present in fibrocartilage and articulating ends of joints (articular cartilage)
CELLS
Embryonic chondrogenic cells – derivatives of mesenchymal cells
Chondroblasts –inner part of perichondrium
Chondrocytes – embedded in extracellular matrix, spherical, deeper localized in cartilage
Ultrastructure of the chondrocytes
In lacunae (as small
chambers)
Territorial and
interterritorial matrix
Dilated cisterns of rough
endoplasmic reticulum, many cisterns of Golgiapparatus, secretoryvesicles - high activityduring production of proteins
Chemical
composition of
hyaline cartilage
IX-Interactions between fibrils and proteoglycan molecules
XI-Regulation of the size of fibrils
X-Organization of collagen fibrils into the 3-dimensional network
Hyaluronan
Chondroitin-sulfate
Keratan-sulfate
Anchorin CII
Majority of water is bound to hyaluronan aggregates – diffusion of metabolites from and into the chondrocytes
Growth of cartilage
Adult organism –growth and regeneration are limited
1) Interstitial growth –mitosis of chondrocytes
2) Appositional growth –differentiation of chondroblasts in inner part of perichondrium
1.
2.
3 types of cartilage – according
arrangement of the cells and
composition of extracellular matrix
Hyaline cartilage: chondrocytes arranged in the
isogenous groups („cell nests“), located in lacunas,
collagen fibrils – collagen II.
Elastic cartilage: chondrocytes arranged mostly
separately, elastic and collagen fibrils – collagen II
Fibrocartilage: chondrocytes arranged separately
or in rows, collagen fibrils – collagen I.
Where can we find a hyaline cartilage?
Maintains airways in respiratory passages (nose, larynx, trachea, bronchi)
Hyaline cartilage – other functions
Development of bones – fetal skeleton
Growth of bones – epiphyseal (growth) plates
Articulation of bones – articular cartilage
Costal cartilages
Articular
cartilage
Hyaline cartilage (glassy)
LACUNAS with CHONDROCYTES
ISOGENOUS GROUPS (cell nests)
NON-VISIBLE FIBERS
(has the same refractive index as
the ground substance)
collagen II.
chondrocyte
hyaluronan
proteoglycan
monomeresHyaline cartilage
Hyaline cartilage
2 regions of the Matrix:
• territorial – matrix around lacuna, few collagen fibers
but rich in chondroitin sulphate → basophilia of the
cytoplasm
• interterritorial – matrix between lacunas
Articular cartilage
Covers the articular surfaces of movable joints
No perichondrium
Exposed to pressure and friction
Tightly connected to the bone, blurred boundary line between cartilage and bone
Without vessels and nerves
Articular capsule
Connective tissue layer
Synovial membrane
Extends folds and villi into cavity, many capillaries, joint cavity is filled by lubricanct –
is derived from blood plasma, high concentration of hyaluronic acid
Synovialocytes A – macrophage-like cells –remove debris from the synovial fluid
Synovialocytes B – fibroblastic synovial cells –produce abundant hyaluronan
Clinical correlations
Degenerative diseases of joints, affecetd principally the articular cartilage
Up to 40% of people older than 70 years suffer from clinically manifested osteoarthrosis of knee joint.
High prevalence of arthritis: immune responses or infectious processes localized in joints (rheumatoid arthritis, tuberculosis)
Microscopic picture of partial damage of articular cartilage 2 months after injury. Locality of damage (D) is healing by the tissue that is not
similar to articular cartilage (DB – damage boundary)
Elastic cartilageAuricle, external auditory
meatus, some cartilages
of larynx, epiglottis
Elastic cartilage
Yellow color – elastic
fibers, collagen type II fibrils
High flexibility
More chondrocytes in
comparison with hyaline
cartilage, more separately
few isogenous groups
perichondrium
Fibrocartilage
• without perichondrium
• thick boundles of
collagenous fibers (I)
• chondrocytes in rows
or separately
Symphysis ossis pubisIntervertebral disc
Fibrocartilage Intervertebral disc
Bone
Strong, hard and
Rigid form of connective tissue
In most areas bone is covered by periosteum
and the central marrow cavity is lined with
endosteum
Bone tissue
protection, support, supply of Ca2+ a PO42-
only 7% of water, many minerals (hydroxyapatite, ions of organic acids)
proteoglycans and glycoproteins (bindingcalcium)
Collagen type I fibers - bone strength
blood vessels and nerves run in canals(Haversian and Volkmann´s canals)
Cells of bone Osteoprogenitor cells: capable of
differentiation and mitotic division
Osteoblasts: produce an osteoid = organic, unmineralized matrix (type I collagen and bone matrix)
Osteocytes: placed in lacunas, connected with each other by their processes, processes placed in canaliculi ossium
Osteoclasts: many nuclei, mononuclear origin (from monocytes), bone resorbtion
Osteoprogenitor cells Derived from mesenchymal stem cells
Located in periosteum and endosteum,
in blood (during bone formation)
Osteoblasts• Produce a bone matrix
• have an ability of mitotic division,
responsible for calcification of bone matrix
• cuboidal or polygonal cells with basophilic cytoplasm, many
rER and GA, arranged into 1 layer – epitheloid arrangement
at the surfaces of bone matrix
Osteocytes
Mature cells, without mitotic activity, are embeded in the bone
Responsible for maintaining the bone matrix
Located in lacunas – via their processes communicate with neighbouring osteocytes, also with osteoblasts and also pericytes of vessels
Are smaller than osteoblasts, less basophilic cytoplasm, connected by nexuses
Osteoclasts Multinucleated cells -
derivated from
mononuclear
precursors
Acidophilic cytoplasm
with many lysosomes
Located in Howship´s lacunas
- ruffled border with microvilli
(hydrolytic enzymes)
Parathormone ↑ activity,
calcitonin ↓ activity of
osteoclasts
Types of bone according their
maturity and structure
Primary bone (immature, woven, nonlamellar):
- during embryonal development, during repair of fractures - random arrangement of collagen fibers
and osteocytes, less minerals
- in dental alveolar bony sockets, insertions of tendons into bones
Secondary bone (mature, lamellar):
- compact bone (diaphysis of long bones - femur)
- spongy – trabecular bone (epiphysis of long bone,
diploe in flat bones of skull...)
Basic morphologic unit of
mature bone is osteon –
Haversian system.
Haversian canal with vessels and nerves
Bone lamellae
Osteocytes in lacunas
Canaliculi ossium
Volkman´s canals
Interstitial, outer and inner
circumferential lamellae
Types of mature bone:
Compact bone
Spongy-trabecular bone
Bone section
Periosteum and
endosteum
Periosteum – composed of outer layer (dense collagen connective tissue) and internal layer (loose collagen connective tissue, osteoprogenitor cells), in both layers - vessels
Endosteum – composed of 1 layer of osteoprogenitor cells, few collagen connective tissue
Function: nutrition of bone tissue and source of bony cells
Sharpey´s perforating fibers
Penetrating collagen fibers from outer layer of periosteum to Haversian system
Formation of bone – general rules
1. Undifferentiated embryonic mesenchymal cells can proliferate and differentiate to osteogenic cells
2. In a highly vascular environment, mesenchymal
cells differentiate to osteoblasts
3. In a poorly vascular environment, mesenchymal
cells form chondroblasts (and cartilage)
4. If calcification occurs around chondrocytes, they
will die leaving empty spaces in lacunae – osteoid tissue will occupy these empty spaces, cartilage models are replaced by bone cells
Bone histogenesis - ossification
Desmogenous (intramembranous)– in embryonal connective tissue -mesenchyme(flat bones of skull, clavicula)
Chondrogenous (endochondral)– in embryonal hyaline cartilage (long and short bones)
Intramembranous ossification
Mesenchymal cells are condensed together in a
highly vascular area where bone formation will
start
Mesenchymal cells proliferate and differentiate
to osteogenic cells – osteoblasts
Osteoid synthesize organic components of the
bone matrix, collagen type I. and osteoid
When osteoblasts are trapped inside lacunase
they are called osteocytes
Bony spicules fuse together as bony trabecules
Endochondral ossification
Replacement of a cartilage model by bone
NOTE! Cartilage does not change to or form bone! Because chondrocytes die and are replace with osteoblasts
Endochondral
ossification –
fundamental steps:
1. Cartilage model of future bone
2. Periosteal bony collar (intramembranous ossification of perichondrium)
3. Proliferation of chondrocytes
4. Hypertrophy of chondrocytes
5. Calcification of extracellular matrix of cartilage and subsequent die of chondrocytes
6. Origin of primary marrow cavity
7. Penetration of the vesselsthrough periosteal bud
8. Formation and storage of an osteoid and its mineralization
Periosteal bony collar (intramembranous ossific. of perichondrium)
Stop of diffusion of oxygen and nutrients into cartilage
Bone growth in width
Proliferation of chondrocytes
Hypertrophy of chondrocytes
Calcification of extracellular matrix – calcified spicules
Penetration of the vessels into periosteal bony collar
Osteoprogenitor cell -osteoblasts (matrix)
Osteoblasts -formation and storage of an osteoid and its mineralization
Osteoclasts – resorption of the matrix
Progress towards the epiphysis
Epiphysis – secondary ossification centre (2)
The same process of ossification as in diaphysis but circular direction
The result –epiphyseal plate
20 years old - epiphyseal closure –stop of the bone growth in the length
Zones in the hyaline cartilage during endochondral
ossification:
I. resting zoneII. proliferative zoneIII. hypertrophic cartilage zoneIV. calcified cartilage zone
-------- V. erosion line -------
VI. ossification zone
future bone
Mineralization of the bone
No satisfactory mechanism can be presented for calcification, two theories exist
Osteoblasts produce alkaline phosphatase,
which could locally increase the deposition of
insoluble calcium phosphate
Osteoblasts produce into bone matrix small matrix vesicules by an active transport
mechanism – formation of calcium phosphate
crystals
Repair of bone after fracture Destruction of bone and haemorrhage,
formation of blood clot
Neutrophils, macrophages – removal of debris
Proliferation of fibroblasts and capillaries into the place of injury = granulation tissue
Formation of connective tissue proper and cartilage in the place of injury – soft, temporary callus
Osteoprogenitors from periosteum and endosteum
– osteoblasts – new, immature bone
Repair of bone after fracture
Vitamins and bone
Vitamin D – promotes calcium and phosphate absorption. Deficiency in children causes the bone disease rickets
Vitamic C – collagen formation. Deficiency results in condition known as scurvy
Vitamin A – ballance between production and resorption of bone
Hormones and bone
Parathormone – activates and increases the number of osteoclasts promoting resorption of bone matrix (raising the blood calcium level)
Calcitonin – decreses the activity of osteoclasts and inhibits bone resorption
Growth hormone – stimulates proliferation of chondrocytes in epiphyseal plate of long bones
Thank you for you attention!
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