Chondrocytes and TMJ Flashcards
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
a type of cartilage containing a higher content of elastic fibers. Found in ear, epiglottis, eustacian tubes
Elastic Cartilage
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
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)
condensation of mesenchymal stem cells into a more dense mass of cells to initiate the formation of a bone rudiment
Mesenchymal Condensation
a process for formation of bone in which a cartilage template is made first, which is then replaced by bone.
Endochondral Bone Formation
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
the joint between the condyle of the mandible (jaw) and the temporal bone of the skull.
Temporomandibular Joint (TMJ)
the major cell type in cartilage which is responsible for producing the cartilage matrix
Chondrocyte
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
a programmed pathway for cell death
Apoptosis
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
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
long unbranched polysaccharides consisting of a repeating disaccharide unit, usually consisting of an amino sugar along with a uronic sugar
Glycosaminoglycan (GAG)
a protein that is heavily glycosylated. Usually consists of a core protein with one or more glycosaminoglycan (GAG) sidechains attached.
Proteoglycan
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
Protein fibers that are predominantly collagen (II, X).•Glossy appearance w/evenly dispersed chondrocytes•Supportive connective tissue•Most abundant type in body-
hyaline cartilage
What type of collagen makes up hyaline cartilage?
2 and 10
has type II collagen together with a lot of elastic fibers (elastin), making it more flexible
Elastic cartilage
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
___ cartilage found in:−Pubic symphysis−Intervertebral disks−Temporomandibular joint (TMJ)
Fibrocartilage
______ cartilage found in pharyngotympanic (eustachian) tubes, epiglottis, and ear lobes
Elastic cartilage
____ 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
Principle engine for longitudinal bone growth is proliferation of ______ and expansion of chondrocyte size (10-15 fold) in _____ region
columnar chondrocytes; hypertrophic
____ 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
more
- 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
