OPBSPathologyMusculoskeletal

Must Know

Synovium is a specialised soft connective tissue lining the inner surface of the joint capsule.
It seals the joint cavity by joining bone, cartilage, capsule and ligament.
It retains synovial fluid and makes the main lubricants, hyaluronan and lubricin (PRG4).
Synovium is vascular, unlike cartilage, so it carries nutrients, waste, immune cells and inflammation.
Synovial fluid is the main metabolic supply for avascular articular cartilage.
Normal fluid holds fewer than 100 leukocytes per mL, mostly monocytes.
Hyaluronan, with serum proteins, gives viscosity. Lubricin lubricates the surface.

Synovial Cells

Feature	Type A	Type B
Nature	Macrophage like	Fibroblast like synoviocyte (FLS)
Origin	Haematopoietic monocyte lineage	Mesenchymal stem cell
Share of resident cells	25 percent	Remainder
Job	Phagocytosis of debris	Secretes hyaluronan and lubricin
Prominent organelle	Mitochondria	Endoplasmic reticulum
Extra	Sits on the inner joint surface	Has some stem cell properties, a cell source for cartilage repair

Synovial Pathology

The joint cavity forms by cavitation of mesenchyme at about 8 weeks of embryonic life.
Synovium covers all joint surfaces except articular cartilage and most fibrocartilage.
The intima is one to two cells thick over a vascular subintima with fat, fibroblasts and histiocytes.
Lining cells lack desmosomes, tight junctions and a basal lamina, which eases exchange with blood.
Synovial-like linings can form away from joints, around failed implants and after surgery (synovial metaplasia).
Villous change is nonspecific. OA shows oedema and mild villous hypertrophy.
Rheumatoid synovium is red, hyperplastic and lymphoplasmacytic, with fibrin rice bodies.
Synovial mesenchymal stem cells have strong chondrogenic potential, relevant to synovial chondromatosis.

Gross colour	Usual cause
Rusty brown	Chronic haemarthrosis, haemophilia, PVNS
Grey synovium, black cartilage	Ochronosis
Black	Metal debris
White foci	Gout, CPPD, calcinosis
Yellow	Xanthoma cells, as in PVNS

Synovial Fluid Analysis

Fluid is a plasma ultrafiltrate enriched with hyaluronan, which gives high viscosity.
Glucose, uric acid and lactate match plasma. Total protein is lower, mostly albumin.
Normal fluid does not clot because it holds little fibrinogen.
Collect into lithium heparin. EDTA chelates calcium and hides CPPD and apatite crystals.
Acetic acid gives a mucin clot. A firm clot means intact hyaluronan.

Feature	Normal	Group I noninflammatory	Group II inflammatory	Group III septic	Group IV haemorrhagic
Knee volume	Under 3.5 mL	Often over 3.5 mL	Often over 3.5 mL	Often over 3.5 mL	Often over 3.5 mL
Viscosity	High	High	Low	Variable	Variable
Colour and clarity	Clear, colourless to straw	Straw to yellow, clear	Yellow to white, cloudy	Yellow-green, opaque	Rusty
White cells per mm3	Under 200	200 to 2,000	2,000 to 75,000	Often 100,000	Variable
Neutrophils	Under 25 percent	Under 25 percent	Often over 50 percent	Over 75 percent	Variable
Mucin clot	Firm	Firm	Friable	Friable	Variable
Culture	Negative	Negative	Negative	Often positive	Negative

Group I includes OA, osteochondritis dissecans, neuropathic joints and osteochondromatosis.
Group II includes RA, SLE, spondyloarthropathy, gout and pseudogout.
Group IV includes haemophilia, anticoagulation, trauma, PVNS and synovial haemangioma.
Cholesterol crystals are square or rectangular plates with notched corners.
Injected steroid can persist as faintly birefringent crystals.

Iron and the Synovium

Blood breakdown leaves haemosiderin in lining cells and subintimal histiocytes.
Iron-laden lysosomes (siderosomes) are seen on electron microscopy.
Iron drives synovial fibroblast proliferation and IL-1, IL-6 and TNF-alpha release.
Haemophilic synovium secretes collagenase and neutral proteinases, even without much inflammation.
Blood coating cartilage also blocks diffusion of nutrients from synovial fluid.
Haemosiderin causes signal loss and blooming on MRI.

Source

Vigorita VJ, Ghelman B, Mintz D. Synovium. In. Vigorita VJ, Ghelman B, Mintz D. Orthopaedic Pathology. 3rd ed. Philadelphia, Wolters Kluwer, 2016.

Crystals in Synovial Fluid

Crystal	Disease
Monosodium urate	Gout
Calcium pyrophosphate	CPPD
Basic calcium phosphate (contains hydroxyapatite)	Osteoarthritis, found in 70 percent of cases

BCP load tracks cartilage loss and acts as a danger signal to fibroblasts, macrophages, chondrocytes and osteoclasts.

Rheumatoid Arthritis

Autoimmune chronic inflammation involving innate and adaptive immunity.
Pannus is hypertrophied synovium that covers, invades and erodes cartilage and bone.
Pannus FLS and macrophages release IL-1 and collagenase.
SDF-1 (CXCL12) rises sharply in RA fluid, less so in OA.
Its receptor CXCR4 sits in the superficial zone of cartilage. Binding triggers MMP-1, 3, 9 and 13.
Synovectomy lowers serum SDF-1, MMP-9 and MMP-13.
RA fluid is turbid, neutrophil rich, larger in volume and lower in viscosity.
T cells and macrophages drive disease through TNF-α, IL-1 and IL-6.

Osteoarthritis and PTOA

Feature	RA synovium	OA synovium
Total immune cells	Higher	Lower
Main cells	Neutrophils in fluid, T cells, macrophages	Macrophages, T cells, mast cells
Cytokines	TNF-α, IL-1, IL-6	IL-1, IL-6, TNF-α

No FDA approved disease modifying OA drug exists.
Chondrocytes, synoviocytes and stem cells show senescence, telomere shortening and SASP in OA.
IL-1, IL-6 and MMPs are the main SASP factors.
TNF-α comes from immune cells in synovium and marrow. Chondrocytes can make IL-1 and IL-6.
Synovitis is mild early, hypervascular mid stage, and thick, villous and fibrotic late.
OA pain correlates with synovitis and bone marrow oedema.
PTOA follows meniscal, ligament, chondral or intra-articular fracture injury and the surgery to fix them.
PTOA has an inflammatory acute phase, a silent interval of days to months, then a chronic phase.
Early synovium after injury shows fibrin, macrophages and leukocytes. Late synovium becomes fibrotic.

Cytokines and Growth Factors

IL-4 and IL-10 are anti-inflammatory, made mostly by lymphocytes and monocytes.
GDF-5 drives joint formation.
TGF-β drives chondrogenesis of stem cells, but in synovium and subchondral bone links to fibrosis and OA.
Excess BMP signalling causes cartilage hypertrophy, osteophytes and heterotopic bone in fibrodysplasia ossificans progressiva.
Lubricin (PRG4) mutation causes autosomal recessive CACP syndrome.
Lubricin is degraded after ACL injury, contributing to PTOA.
Injected IL-1Ra fails in OA, probably from short half-life. Gene therapy gives longer effect.

Drug	Target
Infliximab, golimumab, certolizumab	TNF-α
Tocilizumab, sarilumab	IL-6 receptor
Anakinra	IL-1 receptor antagonist
Canakinumab	IL-1β
Ixekizumab	IL-17A
Ustekinumab	p40 subunit of IL-12 and IL-23
Rituximab	CD20
Tofacitinib	JAK1 and JAK3
Baricitinib	JAK1 and JAK2
Meloxicam	COX-2 over COX-1

Numbers to Remember

Type A cells. 25 percent of resident synovial cells.
Normal fluid leukocytes. Fewer than 100 per mL.
BCP crystals. Present in 70 percent of OA.
PTOA. 12 percent of all OA.
Adult joint injury. 13.9 percent later develop knee OA.

Memory Aids

A for Absorb, B for Build. Type A cells eat debris. Type B cells build hyaluronan and lubricin.
Tofa 1 and 3, Bari 1 and 2. JAK subtypes blocked by each inhibitor.

Exam Traps

Type A cells come from blood monocytes. Type B cells come from mesenchymal stem cells.
RA fluid has more volume but less viscosity.
OA synovium can hold as many mast cells as RA synovium.
CXCR4 is on chondrocytes. SDF-1 is its ligand from synovium.

Related pages. Gout

Source

Chen Q, Gao Y. Synovium and Joint Biology. In. Aaron RK, editor. Orthopaedic Basic Science. Foundations of Clinical Practice. 5th ed. Philadelphia, Wolters Kluwer, 2021.

Practise Type X questions on this topic

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 17 October 2026.