• derangement of normal fibroblast/chondrocyte biosynthesis
• molecule produced can be abnormal, insufficient, or excessive

Acquired (Immunological) Diseases – *connective tissues affected are underlined*

• Systemic Lupus Erythymatosis (SLE) – autoimmune/viral disease involving deposition of immune complexes
• kidney – deposition of immune complexes
• joints – fibrinoid deposition
• skin – follicular plugging/scarring
• vascular – arteriolitis
• immune complex diseases with similar symptoms can be caused by several viruses: sarcoma, coxsackie B, Rauscher LV viruses; also Aleutian mink disease
• Sjorgen’s Syndrome – autoimmune disease involving deposition of immune complex in various organs
• eyes – corneal vascularization
• mouth – parotoid enlargement
• genitourinary – interstitial nephritis
• respiratory – diffuse respiratory fibrosis
• vascular – Raynaud’s phenomenon
• Rheumatoid arthritis – viral disease (virus has not been identified)
• joint – synovial hypertrophy, inflammatory cells (PMN, monocytes, lymphocytes, cartilage erosion, loss of function)
• vascular – perivascular immune complex deposition
• Scleroderma – autoimmune disorder in which fibroblasts over-respond to TGF-b
• normally, TGF-b is produced by platelets and leukocytes during wound healing, causing deposition of ECM
• fibroblasts and chondrocytes respond by producing ECM and producing more TGF-b (amplifying the signal)
• in scleroderma, increased collagen synthesis forms dense network
• skin – thickening and tightening, ulceration, increased pigmentation, calcification
• viscera – heary, lung, kidney, gut fibrosis
• joints – arthritis
• vascular – altered structure and function
• relapsing poly-hondritis – immunological disease
• eye – conjunctivitis, iritis
• cartilage – inflammation of nasal or laryngeal cartilage, pinna of ear

• osteoarthritis – multifactorial (biochemical, biomechanical, cellular) with genetic component
• subacute inflammation produces IL-1 and TNFa that have two effects:
• (1) enhancement of synthesis of: type I collagen, decorin, hemagglutinin, proinflammatory cytokines (PGE₂, IL-6), collagen degradation enzymes (stromelysin/collagenase/plasminogen activator)
• (2) suppression of synthesis of type II collagen, aggrecan, and PAI-1
• the result of this is decreased collagen synthesis and increased degradation
• diarthroidal joints: cartilage degereration, bony sclerosis, osteophytosis (new bone formation)
• mucopolysaccharidosis – biochemical lysosomal storage diseases – Hunter’s and Hurler’s syndromes, Morquio’s disease
• skin, cartilage, vasculature – various effects
• Genetic Collagen Diseases – many different mutations in collagen can lead to disease
• most serious mutation is glycine to hydrophilic residue, or near C-terminus (where fibers form)
• some mutations result in abnormal collagen, others in not enough collagen (intracellular destruction of collagen)
• collagen deficiency leads to weak bones (chicken bone in vinegar) – bowing deformity, secondary pseudoarthritis, etc.
• osteogenesis imperfecta – insufficient or abnormal collagen II Þ thin bones that break very easily (esp. when young)
• two modes of inheritance:
• (1) autosomal dominant – thin bone, Marfan’s syndrome, chondrodystrophia, myositis ossificans myositis
• (2) autosomal recessive – thick bone, homocysteinuria
• variable phenotypes depending upon type (I through IV) – include hearing loss
• long bones – underdevelopment, multiple fractures
• joints – hypermobility/hyperextensibility
• connective tissue – ligaments, tendons, sclera, skin, external ear
• eye – pale blue sclera (cornea so thin can see underlying vasculature)
• Ehlers-Danlos Syndrome – autosomal dominant disease of collagen III (abnormal or insufficient) [type V is sex-linked]
• most mutations result in unstable triple helix, although phenotype dependent upon mutation
• vascular – aneurism
• skin – bruisability
• joints – hypermobility/hyperextensibility
• Collagen-associated molecules
• elastin – stabilized by microfibrillin which is lacking in Marfan’s syndrome leading to weakening of arteries/veins
• affects vascular and connective tissue (abnormal cross-linking, a 2, principally type 3)
• problem is microfibrillin which stabilizes elastin fibers Þ weakening of elastic component of arteries/veins
• proteoglycan – insufficient proteoglycan in bone prior to ossification leads to dwarfism

Treatment – none currently available – put off replacing joints as long as possible (must be redone every five years)