MSK ILS 1: Cartilage & Bone Histology

cartilage

• semi-rigid form of connective tissue

• provides flexibility

• has chondrocytes & ECM [how it differs from connective tissue]

• cells in lacuna, for protection

• avascular [diffusion of nutrients]

• no calcium

  • dysfunctional if calcified

perichondrium

• firmly attached connective tissue layer

• serves as source for new cartilage cell production

• contrains fibroblasts & chondroblasts [progenitor cells] & Type 1 collagen

• vascular layer that feeds chondrocyte & matrix via diffusion

which cartilage does NOT have perichondrium?

articular cartilage

fibrocartilage

isogenous groups

chondrocytes organized into nests of cells

3 types of cartilage

1. hyaline

2. elastic

3. fibrocartilage

hyaline cartilage

• synovial joints, costal cartilage, trachea, nasal cavity

• glassy/transparent appearance & well hydrated

• most abundant

• template for fetal skeleton for later endochondral ossification

• normal calcification of matrix w/ aging

  • osteoarthritis → degeneration of hyaline cartilage

• type II collagen

• resists compression

• proteoglycans [neg charge] hold large amounts of water

capsular matrix

• stains most intensely due to highest conc of matrix components [proteoglycans]

• high metabolic activity

territorial matrix

surrounds an isogenous group

stains less intensely

inter-territorial matrix

stains lightest

is dispersed

Articular cartilage

hyaline cartilage that covers an articular surface of synovial joints

• joint cartilage that persists at joint surface & ends of long bones

• epiphyseal plate

• cartilage does not appear on plain radiographs

  • joint & epiphyseal plate cartilages appear as “gaps” on imaging

epiphyseal plate

• formed by hyaline cartilage

• unossified connective tissue btwn the expanding zones of ossification

• damage → growth defects

elastic cartilage

• external ear, eustachian tube, epiglottis

  • all start with E!

• dark staining

• more flexible

  • few Type II collagen fibers & abundant elastic fibers

• same matrix components of hyaline cartilage

• no calcification during aging

fibrocartilage

• intervertebral discs, pubic symphysis, sternoclavicular joint, temporomandibular joint, menisci of knee joint, tendon insertion

  • midline areas of body

• type I & type II collagen [more fibers than ground substance]

• chondrocytes arranged in rows, dispersed in matrix w/ dense connective tissue

• both chondrocytes & fibroblasts

• damaged hyaline or elastic cartilage is repaired via formation of fibrocartilage

• resists shearing & compression

• acts as shock absorber

fibroblasts make

type I collagen

chondrocytes make

type II collagen

interstitial growth

• cell division of pre-existing chondrocytes

• only occurs during early stages of cartilage formation & in articular cartilage, & the epiphyseal plates of long bones

• increase in length

appositional growth

• differentiation of chondrogenic cells in the perichondrium

• formation of chondroblasts &/or new chondrocytes, which elaborate a new layer of cartilage matrix at the periphery

• increase in width

cartilage calcified in 3 cases

1. articular surface of cartilage in contact w/ bone

2. endochondral ossification [cartilage about to be replaced by bone]

3. hyaline cartilage calcifies as part of aging

osteoarthritis

• degenerative joint disease

• primarily a disease of articular cartilage

• hallmarks

  • ECM degradation

    • enhanced matrix metalloproteinase enzyme activity

  • altered chondrocyte metabolism

• decreased glycosaminoglycan content of matrix & increased water content

• loss of cartilage → bone-bone contact → deterioration of movement & function

  • → bone spurs [osteophytes]

intramembranous ossification

• bone forms directly from mesenchyme

• forms flat bones of skull, most of craniofacial bones, & clavicle

endochondral ossification

• bone forms indirectly from cartilage derived from mesenchyme

• forms most other bones [all long bones of appendicular skeleton]

osteoid

uncalcified matrix of proteoglycans & type I collagen fibers

alkaline phosphatase

induces mineralization of osteoid via precipitation of inorganic calcium phosphate salts [Hydroxyapatite]

cannaliculi

extend from each osteocyte in its lacuna & facilitate communication via gap junctions

trabeculae

fused spicules of dvlping bone form

• spongy bone [bone marrow]

primary ossification center

• dvlps at middle of diaphysis of hyaline cartilage model, containing type II collagen

secondary ossification center

• Develops in proximal & distal epiphysis of long bones

• w/ continued growth of long bone, the distal epiphyseal cartilage disappears

• w/ cessation of growth, the proximal epiphyseal cartilage disappears

• metaphysis becomes continuous w/ the epiphysis

  • epiphyseal lines remain where epiphyseal plate last existed

achondroplasia

• mutation → overactive FGFR3 → excessive inhibition of chondrocyte proliferation

  • → impaired endochondral ossification

    • → short staure

      • *normal head size bc thats a primary ossification center

Epiphyseal plate: zones of ossification [superior to inferior]

• zone of reserve cartilage [resting]

• zone of proliferation

• zone of hypertrophy

• zone of calcification

• zone of resorption

zone of reserve cartilage [resting]

no cellular proliferation or prod. of matrix

zone of proliferation

• chondrocytes divide & produce more cells that are larger

• cells organize into columns

zone of hypertrophy

enlarged chondrocytes secrete collagen & encourage vascular invasion

zone of calcification

cells degenerate & matrix becomes calcified

zone of resorption

small vessels & osteoprogenitor cells migrate to newly calcified region

volkmann’s canal

• connects 2 diff. haversian canals

• connect to periosteum, endoesteum & carry the neurovascular supply

spongy bone

also called cancellous bone

• found inside

• esp in epiphysis

*osteoporosis typically affects spongy bone first [compact bone usually affected mid shaft]

periosteum

outer fibrous layer of connective tissue [dense]

• distributes BVs to bone

• contains many sensory nerves

  • v. painful

• v. similar to perichondrium

• helps w/ adherence

• thicker in children

  • heal fractures quicker

• vital to bone survival

sharpey fibers

• type I collagen fibers

• attach periosteum to bone surface

endosteum

inner layer of connective tissue w/o fibers

• lines marrow cavities & supplies osteoprogenitor cells that can differentiate into osteoblasts

haversian canal

• contain BVs, nerves, & loose connective tissue

• in compact bone from lamellae organization

• lined by osteoprogenitor cells & osteoblasts

*in osteomyelitis, infection within bone, can spread thru haversian canals

osteoclasts

resorb & remodel bone

• come from a diff lineage of cells

  • hematopoeitic progenitor [mononuclear-phagotcyte system]→ inactive osteoclast → active

    • blood-borne monocytes

• large, motile, multinucleated

• ruffled border

• found in resorption cavities [Howship lacunae]

other bone cells [bone-building lineage]

mesenchymal → osteoprogenitor → osteoblast → osteocyte → bone-lining cell

bone lining cells [periosteal cells

flat cells present on surface of bone where no active growth or resorption is occuring

markers of bone activity

• presence of hydroxyproline [from digestion of collagen] in urine

  • hight osteoclastic activity

• bone-specific alkaline phosphatase [BSAP]

  • released during osteoid formation & mineralization

    • high osteoblastic activity

• Howship’s lacunae [resorption bay]

  • not same as lacunae in which osteocytes are found

osteoporosis

• more bone resorption than bone deposition

• worsened by estrogen deficiency [post-menopausal women]

• hormone replacement therapy slows rate of bone loss

• calcitonin also inhibits bone resorption

osteomyelitis

• inflammation of bone & bone marrow caused by many pathogens

• can enter bone via blood stream, injury, or contiguous spread from infection in adj. tissue

• ex. prosthetic joint replacement, root canal therapy, internal fixation of bone fractures

• common causative pathogens:

  • Staphylococcus aureus

  • MRSA

• treatment

  • prolonged antibiotic therapy

  • surgery

osteophytes

bone spurs

• in fingers and toes, known as Heberden [distal interphalangeal joint] or Bouchard nodes [proximal interphalangeal joint]

• treatment

  • PT

  • analgesic meds

  • surgery

osteogenesis imperfecta

• hereditary disorder: bone fragility, deformability, recurrent fractures w/ 4 clinical subtypes

• abnormalities in type I collagen

• higher # of osteoblasts, but their activity is greatly reduced

• features:

  • deformities

  • short stature

  • recurrent fractures [w/minimal trauma]

  • blue sclera

  • hearing loss

  • dental issues

paget disease [osteodytrophia deformans]

• chronic disorder of excessive bone resorption & abnormal bone formation

  • increased osteoclastic AND osteoblastic activity

• → enlarged, misshapen, brittle bones prone to fracture

• most often seen in middle-aged to elderly men

• biopsy shows small, irregular fragments of bone matrix united in a jigsaw or mosaic pattern

• may be caused by slow viral infection or genetic mutations of genes on chromosome 5

• pts. at risk of osteoarthritis

• enlargement of skull → headache & hearing loss

• bowed leg, shin deformity, increased hat size, increase shoe size, increased wing size

• painful

• difficult to heal fractures

• diagnosis

  • alkaline phosphatase [ALP] levels HIGH

  • x-rays

    • bone deformation w/ sclerotic & osteolytic lesions

osteomalacia & rickets

adults vs children

• metabolic bone disorder caused by vitamin D deficiency

• excessive amounts of unmineralized osteoid tissue [soft bone]

• in children w/ rickets this presents at the epiphyseal growth plates → bowed legs, deformed skull & ribs

• diagnostic

  • low Vit D

  • low calcium

  • low phosphate

  • high ALP

  • x-rays shows fractures, widened growth plate in children, bending of bone

• treatment

  • vit D & calcium supplement

  • sunlight exposure

osteopetrosis

• rare heriditary bone disease in which failure of osteoclastic bone resorption → increased bone mass

• diagnosed in early infancy

• 3 distinct forms of the disease based on age & clinical features

• greater bone fragility comes from defective remodeling of woven bone to compact bone

• fatal if untreated

  • → cranial nerve compression, hepatosplenomegaly

• potential therapy: hematopoeitic stem cell or bone marrow transplant from allogenic donor

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