Specialized Connective Tissue: Cartilage

Specialized Connective Tissue and ECM: Cartilage

• Connective tissues have reduced cellular content and increased extracellular matrix (ECM) content, compared to epithelial, muscle, and nervous tissue.
• ECM is the main stress-bearing component of connective tissues, and facilitates cell-cell contact indirectly.

Composition of the ECM

• ECM is a network of fibrous proteins and hydrated proteoglycans that surround cells in tissues.
• It strengthens and supports tissues, guides cell migration and polarity, transports nutrients and waste, and permits intercellular communication.
• ECM maintenance requires a balance between synthesis and breakdown of its components; it is not a static framework.

Cartilage Types

• Hyaline cartilage: Found in ribs, nose, larynx, trachea, and articular joints.
• Fibrocartilage: Found in joint capsules, ligaments. (Least flexible, fewest cells, highest collagen content).
• Elastic cartilage: Found in ear, epiglottis, and larynx.

Cartilage Structure and Function

• Articular cartilage is a type of hyaline cartilage, specifically found in joints.
• It's vital for load-bearing and joint movement. It's critical that the articular cartilage structure maintains its integrity for normal function.
• Composed primarily of collagen (type II) and aggrecan, these are vital for strength and support.
• Loss of collagen integrity leads to loss of matrix strength.

Collagen Biosynthesis

• Collagen synthesis occurs in a series of steps, beginning in the rough endoplasmic reticulum, continuing through various Golgi modifications, and concluding with extracellular fiber formation.
• Essential for the formation of the cartilage matrix.

Ehlers-Danlos Syndrome

• A genetic condition caused by defective collagen deposition.
• Results in hyperextensible joints.

Diseases Associated with Collagen Mutations

• Various diseases arise from mutations in collagen genes or collagen-processing enzymes, which significantly impact collagen's structure and function.

Aggrecan (Complex PG)

• A crucial part of the cartilage ECM.
• Composed of a core protein, link proteins, and various glycosaminoglycans (GAGs), specifically chondroitin sulfate and keratan sulfate, which are bound to the core protein.
• Hyaluronic acid forms a large molecule outside of the complex, which contributes substantially to a gel-like consistency of the cartilage.
• GAGs' negative charges attract and bind a large amount of water, which leads to the hydrated gel found in cartilage and enables load-bearing.

Chondrocytes

• Adult cartilage is largely composed of only this single cell type.
• They represent 5-10% of the ECM volume.
• They are large and mature, found in groups of 2-8 cells.
• They are rich in RER and Golgi, and secrete high amounts of type II collagen and aggrecan.
• They are avascular, lymphatic, and non-neuronal.
• They differentiate from mesenchymal stem cells (MSCs) during embryonic development, and are vital in creating the extracellular matrix.
• Highly specialized cells that have a particular importance in chondrocyte proliferation, ECM synthesis, and cartilage formation.

MSC Differentiation to Chondrocytes

• Differentiate into chondrocytes during embryonic development from MSCs.
• ECM components for cartilage are secreted by them.
• Key transcription factors like Sox-9 are crucial.
• Various growth factors, including TGF-β, fibroblast growth factor (FGF), insulin-like growth factor (IGF-1), and parathyroid hormone-related protein (PTHrP), are required for proliferation and ECM synthesis.

Bone Formation (Ossification)

• Chondrocytes are crucial for the formation of bone from the cartilage model, specifically with endochondral ossification during fetal development, especially with bones such as the long bones.
• The cartilage model is substituted by bone.
• Primary ossification centers are established first in long bones.
• Secondary ossification centers appear in epiphyses later.
• Hyaline cartilage is deteriorated, and a cartilage matrix is created with spongy bone formation at the primary ossification centers.
• Later, blood vessels and cells invade the cartilage matrix to drive ossification further.
• The cartilage model is replaced by new bone matrix.

Inductive Signaling (Spatial patterning of chondrocytes during bone formation)

• Morphogens, such as IHH and PTHrP, influence chondrocyte location and fate.
• Signaling molecules pass between cells through the developing ECM, resulting in different chondrocyte proliferation and death rates in various locales.
• For example, hedgehog family proteins like IHH and Sonic hedgehog (Shh) play a crucial role, maintaining chondrocyte proliferation in specific locations.