Chondrocytes and TMJ Flashcards by Michael McMahan

the most abundant type of cartilage, which has large fibers of predominantly collagen (type II [and X in hypertrophic regions]) and evenly dispersed chondrocytes. Found in growth plate, articular surfaces of joints, costal cartilage and as a supportive tissue in nose, ears, trachea, etc.

Hyaline Cartilage

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a type of cartilage containing a higher content of elastic fibers. Found in ear, epiglottis, eustacian tubes

Elastic Cartilage

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a type of cartilage containing finer collagen fibers in layered arrays with a spongy appearance. Contains both type I and type II collagen. Found in pubic symphysis, intervertebral disks, temporomandibular joint

Fibrocartilage

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a multipotent stem cell that has the capacity to differentiate into a variety of cell types, including osteoblasts, muscle cells, adipocytes, chondrocytes.

Mesenchymal Stem Cell (MSC)

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condensation of mesenchymal stem cells into a more dense mass of cells to initiate the formation of a bone rudiment

Mesenchymal Condensation

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a process for formation of bone in which a cartilage template is made first, which is then replaced by bone.

Endochondral Bone Formation

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cartilage in which the chondrocytes have undergone hypertrophy. This includes swelling of the cell volume, mineralization of the surrounding matrix, expression of marker genes of hypertrophy. In the final stages, the hypertrophic chondrocytes will undergo apoptosis.

Hypertrophic Cartilage

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the joint between the condyle of the mandible (jaw) and the temporal bone of the skull.

Temporomandibular Joint (TMJ)

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the major cell type in cartilage which is responsible for producing the cartilage matrix

Chondrocyte

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a chondrocyte that has undergone hypertrophy (swelling in size, deposition of mineral in the surrounding matrix, expression of late chondrocyte markers). The cell will eventually undergo apoptosis.

Hypertrophic Chondrocyte

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a programmed pathway for cell death

Apoptosis

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the cartilage that remains between the metaphysis (neck) of the bone and the rounded ends of the bone at the ends (epiphyses). This cartilage allows the longitudinal growth of bones. It is also called the epiphyseal plate.

Growth Plate

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hereditary skeletal disorders characterized by abnormal growth plate function, which leads to skeletal deformities/growth defects – often dwarfism. (note – sometimes skeletal dysplasia or osteochondrodysplasia are used somewhat interchangeably. These terms include dysplasias of cartilage and bone).

Chondrodysplasias

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long unbranched polysaccharides consisting of a repeating disaccharide unit, usually consisting of an amino sugar along with a uronic sugar

Glycosaminoglycan (GAG)

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a protein that is heavily glycosylated. Usually consists of a core protein with one or more glycosaminoglycan (GAG) sidechains attached.

Proteoglycan

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specialized connective tissue that is avascular and has limited regenerative; contains gelatinous ground substance (mostly proteoglycans); collagen and elastic protein fibers are embedded in ground substance; found in locations where support flexibility, resistance to compression

cartilage

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Protein fibers that are predominantly collagen (II, X).•Glossy appearance w/evenly dispersed chondrocytes•Supportive connective tissue•Most abundant type in body-

hyaline cartilage

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What type of collagen makes up hyaline cartilage?

2 and 10

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has type II collagen together with a lot of elastic fibers (elastin), making it more flexible

Elastic cartilage

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mixture of fibrous tissue (type I collagen containing) and hyaline cartilage; Chondrocytes dispersed among fine collagen fibers in layered arrays; Spongy (good shock absorber) -•ECM of fibrocartilage contains both type I and type II collagen

Fibrocartilage

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___ cartilage found in:−Pubic symphysis−Intervertebral disks−Temporomandibular joint (TMJ)

Fibrocartilage

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______ cartilage found in pharyngotympanic (eustachian) tubes, epiglottis, and ear lobes

Elastic cartilage

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____ cartilage found in Growth plate, Precursor to bone in embryonic skeleton, Joint articular surfaces (reduces friction/acts as shock absorber), Costal (rib) cartilages, and Cartilage in nose, ears, trachea, larynx, smaller respiratory tubes

hyaline cartilage

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Principle engine for longitudinal bone growth is proliferation of ______ and expansion of chondrocyte size (10-15 fold) in _____ region

columnar chondrocytes; hypertrophic

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____ is the master regulator in chondrocyte differentiation

SOX9

SOX9, RUNX2, and Osterix are _____ involved in chondrocyte differentiation

transcription factors

IHH, PTHrP, FGFs and VEGF are _____ involved in chondrocyte differentiation

signaling molecules

PTC1, FGFR3, and PTH1R are _____ involved in chondrocyte differentiation

receptors for signaling molecules

COL2A1, ACAN, and COL10A1 are _____ involved in chondrocyte differentiation

ECM components

TNSALP and MMP13 are _____ involved in chondrocyte differentiation

enzymes/proteases

drives differentiation down chondrocyte pathway •Expressed in chondroprogenitors/ proliferating chondrocytes (not hypertrophic chondrocytes)

Master transcription factor

must be downregulated to allow chondrocytes to mature; ______ inhibits RUNX2)

SOX 9

Expressed in pre-hypertrophic and hypertrophic chondrocytes•Important regulators of hypertrophy

RUNX2/OSX

What do chondrocytes express when they hypertrophy?

type X collagen, alkaline phosphatase, and MMP13/VEGF

____ and _____ are key regulators of chondrogenesis

IHH and PTHrP

Co-ordinated actions of Ihh and PTHrP signaling through their receptors ____ and ____ regulate chondrocyte proliferation/differentiation and determine length of the proliferating columns of chondrocytes

PTC1 and PTH1R

____ axis is very important in regulating bone longitudinal bone growth

Ihh/PTHrP

_____ Regulatory Loop Controls Chondrocyte Differentiation Kinetics

Ihh/PTHrP

critical regulator of chondrocyte proliferation/differentiation

FGF signaling

_____ signaling very important additional regulatory step that limits chondrocyte proliferation that also suppresses IHH

FGFR3

Type ___ collagen is the major fibrillar collagen in cartilage

Type 2 collagen

___ is a Homotrimer of α1(II) chains (encoded by COL2A1gene)

Type 2 collagen

Major collagen expressed in hypertrophic cartilage

Type 10 collagen

Homotrimer of α1(X) chains (encoded by COL10A1gene)

Type 10 collagen

unbranched polysaccharide chains composed of repeating disaccharide units; usually highly sulfated making it negatively charged

GAGs

1st sugar residue in a GAG is an ____ sugar

amino sugar

2nd sugar residue in a GAG is ____

uronic acid

hyaluronan, chondroitin sulfate and dermatan sulfate, heparan sulfate and heparin, and keratan sulfate are the main groups of ____

GAGs

Most GAGs are found covalently attached to a protein core in the form of _____

proteoglycans

What are the 2 major proteoglycans of skeletal tissues?

Aggrecan and versican

Major proteoglycan in cartilage that is produced in large amounts by proliferating and prehypertrophic chondrocytes; core has keratan sulfate and chondroitin sulfate GAG chains

aggrecan

Assembles with hyaluronan to form huge aggregates; binds high amounts of water due to negative charge; may regulate calcification

aggrecan

hereditary skeletal disorders characterized by abnormal growth plate function leading to skeletal deformities/growth defects

chondrodysplasias

Rare human syndrome caused by heterozygous loss of function in SOX9 that is autosomal dominant that affects development of skeleton/reproductive system

Camplomelic dysplasia

____ leads to late proliferating/prehypertrophic chondrocytes will enter into hypertrophy too soon leading to growth retardation

impaired PTHrP signaling

___ leads to no replacement of proliferating cell once they have gone into hypertrophy leading to growth retardation

impaired IHH signaling

Inactivating mutations in PTH1R cause

Blomstrand Lethal Chondrodysplasia

Activation mutations in PTH1R cause

Jansen's metaphyseal chondrodysplasia (Eiken syndrome)

Inactivating mutations in PTHrP cause

Brachydactyly type E2

Inactivating mutations in IHH cause ___ and ___

Brachydactyly type A1 and Acrocapitofemoral Dysplasia

Activating point mutations in FGFR3 in humans are associated with ____ characterized by shortened disorganized columns of chondrocytes in growth plate

Achondroplasia

Most common form of short limbed dwarfism; caused by activating mutations in FGFR3 gene; autosomal dominant; homozygotes have severe disease that are usually still born or die shortly after birth from respiratory failure

Achondroplasia

Short stature w/ disproportionately short limbs (trunk relatively normal)•Short fingers/toes•Large head/prominent forehead•Small midface/flattened nasal bridge•Spinal kyphosis (convex curvature) or lordosis (concave curvature)•Varus (bowleg) or valgus (knock knee) deformities are all features of ___

Achondroplasia

achondrogenesis type II/hypochondrogenesis are ____- mutations to collagen 2

Lethal-

spondyloepiphyseal dysplasia (SED), spondyloepimetaphyseal dysplasia congenita, Marshall syndrome are ____ mutations to collagen 2

Severe-

Stickler syndrome and early onset osteoarthritis are ____ mutations to type 2 collagen

Mild-

-short, barrel-shaped trunk-very short extremities-large head, soft cranium-flat face-underossificationof the vertebral bodies and pelvis-hypercellularepiphyseal cartilage-poorly organized or absent growth plate-diminished extracellular matrix-thick, irregular collagen fibrils are characteristics of ______

Achondrogenesis type 2

Replacement of glycine by a bulkier amino acid in triple helical region of alpha1 (II) chain

Achondrogenesis type 2

Mutations in COL2A1gene•Autosomal dominant•Short stature from birth - height reaches 2– 4.5ft•Kyphoscoliosis(curved spine) / vertebral defects (e.g. flattened vertebrae)•Short trunk, neck, limbs•Hands/feet less affected•Hip deformities/clubfoot are characteristic of ____

Spondyloepiphyseal dysplasia (SED)

Mutations in COL10A1gene •Short stature, bowing of the long bones, widening/irregularity of growth plates

Schmid-type metaphyseal chondrodysplasia

_____ has cushioning function - prevents bone on bone wear)•Splits joint into two synovial joint cavities

articular disk

Articular surfaces of bones covered in ____ rather than hyaline

fibrocartilage

TMJ enclosed in a ______

fibrous capsule

Upper head of _____ muscle inserts onto articular disk

lateral pterygoid

fibrous/avascular (fibrocartilage)•Composed of dense fibrous tissue containing−Tightly packed collagen fibers−Proteoglycans−Elastic fibers

Articular disk in TMJ

Central part of articular disk is ____

avascular

TMJ disorders are ____ prevalent in women than men

- thought to be a multifactorial process secondary to muscle hyperfunction, traumatic injuries, hormonal influences, articular changes (e.g. osteoarthritis) •Malocclusion thought to be a contributing factor•Symptoms = decreased mandibular range of motion, muscle/joint pain, functional limitation/deviation of the jaw opening.

Temporomandibular disorder (TMD)

TMJ disorders are divided into what 2 types?

articular disorders and non articular disorders

____ most common TMJ arthropathy –as disc is forced out of alignment, can lead to bone on bone contact if disc degenerates (wearing of joint surfaces)

Disc displacement