Comparison of knee joint and temporomandibular joint development in pig embryos.

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

The anterolateral ligament of the knee is not a solid structure in human fetuses.

PURPOSE: The purpose of this study was to investigate if the anterolateral ligament of the knee (ALL) is present in the human fetus and describe its topography along with other structures of the region. METHODS: Forty human fetuses knee joints, at mean age 34 weeks (± 2.57 weeks), fixed in 10% formalin, were submitted to cross-sectional dissection and mesoscopic analysis. RESULTS: The ALL was not identified, although the usual topography of the region was identified in all specimens: skin, subcutaneous tissue, iliotibial tract (ITT), fibular collateral ligament, popliteal muscle tendon, lateral meniscus, patellar ligament, infrapatellar fat pad, lateral patellar retinaculum, knee joint capsule, lateral inferior genicular vessels, and the biceps femoris tendon. The ITT reveals anterior (n = 12) and lateral thickening (n = 17) in some specimens. This thickening was found in both knees of the same subject in 6/20 specimens. CONCLUSION: The anterolateral ligament of the knee is not a congenital or solid structure. Our results suggest that the ALL may be a deep layer of the ITT or part of the knee joint capsule, or its identification is evaluator dependent.

Popliteal Artery Entrapment Syndrome.

¼ Popliteal artery entrapment syndrome is a commonly misdiagnosed condition that should be considered in patients presenting with exertional lower-extremity pain. ¼ In addition to a focused physical examination, the ankle-brachial index and advanced imaging consisting of computed tomography and computed tomographic angiography or magnetic resonance imaging and magnetic resonance angiography are crucial in evaluating the underlying cause of entrapment. ¼ Consultation with a vascular surgeon or team is necessary when planning surgical treatment of popliteal artery entrapment syndrome.

Morphological structure and variations of fetal lateral meniscus: the significance in convenient diagnosis and treatment.

PURPOSE: The aim of this study is to evaluate of morphometry of the lateral meniscus (LM) and determine incidence of the LM shapes. METHODS: This study was performed on fetal cadaver collection of Anatomy Department of Necmettin Erbakan University. Fifty human fetal cadavers (25 female, 25 male human fetal cadavers) were used in this study. Microdissection was performed. Morphometric measurements were performed. LM were classified into four types and five subtypes. RESULTS: In this study, it was identified that all parameters which were measured were found to be increased with gestational ages. Four morphological types and five morphological subtypes were determined. It was found that 12% of the LM were crescent-shaped, 66% of the LM were C-shaped, 14% of the LM were incomplete-disc-shaped, 2% of the LM were disc-shaped, 6% of the LM were variant C-shaped. CONCLUSIONS: A few studies on fetal meniscal anatomy and its development were performed. Each new study is important for having detailed anatomy and development of the fetal menisci which will have both clinical and anatomical impacts during childhood and adulthood for orthopedic surgeons and anatomists, respectively. The most important results of this study were the detailed objective analysis of the macroscopic fetal growth of LM. It was significantly observed that four morphological types and five morphological subtypes of LM. The results of the present study related with both the observation of morphological development of the fetal meniscal anatomy, and its morphological variants, are important in terms of improving our knowledge, and clinical approach on the description, and the management of the symptomatic lateral discoid meniscus tears in children, adolescents, and adults. The clinical relevance of this study was that this classification of fetal menisci could ameliorate our current understanding of the morphology of lateral meniscus in adult, further.

Prenatal growth map of the mouse knee joint by means of deformable registration technique.

Joint morphogenesis is the process during which distinct and functional joint shapes emerge during pre- and post-natal joint development. In this study, a repeatable semi-automatic protocol capable of providing a 3D realistic developmental map of the prenatal mouse knee joint was designed by combining Optical Projection Tomography imaging (OPT) and a deformable registration algorithm (Sheffield Image Registration toolkit, ShIRT). Eleven left limbs of healthy murine embryos were scanned with OPT (voxel size: 14.63µm) at two different stages of development: Theiler stage (TS) 23 (approximately 14.5 embryonic days) and 24 (approximately 15.5 embryonic days). One TS23 limb was used to evaluate the precision of the displacement predictions for this specific case. The remaining limbs were then used to estimate Developmental Tibia and Femur Maps. Acceptable uncertainties of the displacement predictions computed from repeated images were found for both epiphyses (between 1.3µm and 1.4µm for the proximal tibia and between 0.7µm and 1.0µm for the femur, along all directions). The protocol was found to be reproducible with maximum Modified Housdorff Distance (MHD) differences equal to 1.9 µm and 1.5 µm for the tibial and femoral epiphyses respectively. The effect of the initial shape of the rudiment affected the developmental maps with MHD of 21.7 µm and 21.9 µm for the tibial and femoral epiphyses respectively, which correspond to 1.4 and 1.5 times the voxel size. To conclude, this study proposes a repeatable semi-automatic protocol capable of providing mean 3D realistic developmental map of a developing rudiment allowing researchers to study how growth and adaptation are directed by biological and mechanobiological factors.

Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis.

OBJECTIVES: Given the role of growth and differentiation factor 5 (GDF5) in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from Gdf5 loss of function and how its regulatory regions control knee formation and morphology. METHODS: The brachypodism (bp) mouse line, which harbours an inactivating mutation in Gdf5, was used to survey how Gdf5 loss of function impacts knee morphology, while two transgenic Gdf5 reporter bacterial artificial chromosome mouse lines were used to assess the spatiotemporal activity and function of Gdf5 regulatory sequences in the context of clinically relevant knee anatomical features. RESULTS: Knees from homozygous bp mice (bp/bp) exhibit underdeveloped femoral condyles and tibial plateaus, no cruciate ligaments, and poorly developed menisci. Secondary ossification is also delayed in the distal femur and proximal tibia. bp/bp mice have significantly narrower femoral condyles, femoral notches and tibial plateaus, and curvier medial femoral condyles, shallower trochlea, steeper lateral tibial slopes and smaller tibial spines. Regulatory sequences upstream from Gdf5 were weakly active in the prenatal knee, while downstream regulatory sequences were active throughout life. Importantly, downstream but not upstream Gdf5 regulatory sequences fully restored all the key morphological features disrupted in the bp/bp mice. CONCLUSIONS: Knee morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression in knee tissues. This downstream region contains numerous enhancers harbouring human variants that span the osteoarthritis association interval. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus' role in osteoarthritis risk.

The anterolateral ligament: A cadaveric study in fetuses.

The aim of this study was to determine the presence and morphology of the anterolateral ligament (ALL) of the knee in a sample of fetuses. We hypothesized that the ALL is present in sample fetuses and its origin is not related to repetitive stresses throughout life. Forty fresh-frozen knees from cadaveric fetuses were dissected using a standard technique. The ALL and other structures in the anterolateral compartment of the knee were identified. The details of the femoral and tibial attachments, course and relationships with anatomical structures of the ALL were identified, recorded, and quantitatively characterized. The ALL was identified in 100% of the dissected knees. We found three anatomical patterns regarding the femoral attachment: (1) Proximal and posterior to the fibular collateral ligament (55%); (2) Together with the fibular collateral ligament (25%); and (3). Anterior and distal to it (20%). The ALL was extracapsular with an oblique course attaching into the anterolateral aspect of the tibia, midway between the midpoint of Gerdy's tubercle and the fibular head. The ALL has a strong attachment to the lateral meniscus, creating two fascicles: proximal or meniscofemoral and distal or meniscotibial. The ALL is a constant, extracapsular anatomical structure in the anterolateral compartment of the knee, present from the later prenatal period of life. Its morphology shows three different patterns of femoral attachment in relation to the fibular collateral ligament position, a strong attachment in the lateral meniscus, and a constant tibial attachment. Clin. Anat. 30:625-634, 2017. © 2017 Wiley Periodicals, Inc.

Anatomic and Histological Investigation of the Anterolateral Capsular Complex in the Fetal Knee.

BACKGROUND: There is currently disagreement with regard to the presence of a distinct ligament in the anterolateral capsular complex of the knee and its role in the pivot-shift mechanism and rotatory laxity of the knee. PURPOSE: To investigate the anatomic and histological properties of the anterolateral capsular complex of the fetal knee to determine whether there exists a distinct ligamentous structure running from the lateral femoral epicondyle inserting into the anterolateral tibia. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty-one unpaired, fresh fetal lower limbs, gestational age 18 to 22 weeks, were used for anatomic investigation. Two experienced orthopaedic surgeons performed the anatomic dissection using loupes (magnification ×3.5). Attention was focused on the anterolateral and lateral structures of the knee. After the skin and superficial fascia were removed, the iliotibial band was carefully separated from underlying structures. The anterolateral capsule was then examined under internal and external rotation and varus-valgus manual loading and at different knee flexion angles for the presence of any ligamentous structures. Eight additional unpaired, fetal lower limbs, gestational age 11 to 23 weeks, were used for histological analysis. RESULTS: This study was not able to prove the presence of a distinct capsular or extracapsular ligamentous structure in the anterolateral capsular complex area. The presence of the fibular collateral ligament, a distal attachment of the biceps femoris, the entire lateral capsule, the iliotibial band, and the popliteus tendon in the anterolateral and lateral area of the knee was confirmed in all the samples. Histological analysis of the anterolateral capsule revealed a loose, hypocellular connective tissue with less organized collagen fibers compared with ligament and tendinous structures. CONCLUSION: The main finding of this study was that the presence of a distinct ligamentous structure in the anterolateral complex is not supported from a developmental point of view, while all other anatomic structures were present. CLINICAL RELEVANCE: The inability to prove the existence of a distinct ligamentous structure, called the anterolateral ligament, in the anterolateral knee capsule may indicate that the other components of the anterolateral complex, such as the lateral capsule, the iliotibial band, and its capsule-osseous layer, are more important for knee rotatory stability.

A new insight into the fabella at knee: the foetal development and evolution.

Using longitudinal semiserial sections of 12 lower extremities from 8 human foetuses at 15-18 weeks, we compared foetal morphologies of the knee in specimens with and without fabellae. We also compared the fabella, if present, with the hallucal sesamoid in the same foetus. Cartilaginous fabella, positive for versican and tenascin by immunohistochemistry, was found in 5 of the 8 foetuses. This structure was embedded in a thick and tight lateral fibrous band, providing a common origin of the plantaris muscle and the lateral head of the gastrocnemius muscle. The plantaris was covered by the lateral head of the gastrocnemius, but these 2 muscles were separated by a distinct fascia or space. Notably, the foetal fabella did not attach to the joint capsule. In the 3 specimens without fabellae, the lateral fibrous band was thin, containing a fibrous mass, negative for versican and tenascin, in place of the fabella. The "medial" head of the gastrocnemius faced or covered the plantaris, while the lateral head was continuous with the plantaris. A hallucal cartilaginous sesamoid, positive for versican and tenascin, was present in all 8 specimens. It carried a flat surface facing the joint cavity and was covered by tendons of the short muscles of the foot. Because of the difference in topographical relation of muscles between specimens with or without fabella, rather than mechanical stress to the tendon, fabella development may require a distinct plantaris muscle independent of the gastrocnemius. We discussed about an evolutionary aspect of the fabella and plantaris muscle.

Three-dimensional reconstruction of rat knee joint using episcopic fluorescence image capture.

OBJECTIVE: Development of the knee joint was morphologically investigated, and the process of cavitation was analyzed by using episcopic fluorescence image capture (EFIC) to create spatial and temporal three-dimensional (3D) reconstructions. METHODS: Knee joints of Wister rat embryos between embryonic day (E)14 and E20 were investigated. Samples were sectioned and visualized using an EFIC. Then, two-dimensional image stacks were reconstructed using OsiriX software, and 3D reconstructions were generated using Amira software. RESULTS: Cavitations of the knee joint were constructed from five divided portions. Cavity formation initiated at multiple sites at E17; among them, the femoropatellar cavity (FPC) was the first. Cavitations of the medial side preceded those of the lateral side. Each cavity connected at E20 when cavitations around the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were completed. CONCLUSION: Cavity formation initiated from six portions. In each portion, development proceeded asymmetrically. These results concerning anatomical development of the knee joint using EFIC contribute to a better understanding of the structural feature of the knee joint.

'The Sneaky Plica' revisited: morphology, pathophysiology and treatment of synovial plicae of the knee.

PURPOSE: To comprise current knowledge on morphology, embryology and pathophysiology of synovial plicae as well as on clinical and therapeutic aspects of the plica syndrome. METHODS: Review of the literature combined with a meta-analysis of studies assessing the outcome of open or arthroscopic plica excision including the author's own series. RESULTS: The term synovial plica has been devised to describe a number of intra-capsular folds thought to represent remnants of a membranous knee joint partition present during foetal development. Although four such folds have been defined, it is mainly the medial patellar plica which is implicated in carrying clinical significance as a potential cause of anteromedial knee pain particularly in adolescents. Blunt trauma, a sudden increase in athletic activity or any form of transient synovitis are associated with plica inflammation leading to tissue fibrosis and subsequent loss of elasticity. A plica affected in this way may impinge against intra-articular structures in its proximity, often creating localised chondromalacia particularly of the patello-femoral joint. The diagnosis is based on history and clinical examination although MRI can be of value. Twenty-three studies assessing the clinical out-come of 969 patients following open or arthroscopic plica excision were identified. The average age was 25 years with equal male-to-female ratio. Trauma was considered the cause in 57 %. At a mean follow-up of 27.5 months, 64 % of patients were symptom free, 26 % improved and 10 % considered failures. CONCLUSION: Symptomatic plicae may initially be treated with physiotherapeutic measures and structured exercise regimes but success rates are generally low. Intra-plical or intra-articular corticosteroid injections may be beneficial if administered early in the disease process. Arthroscopic excision of the entire plical fold becomes indicated in recalcitrant cases and once a plica has undergone irrevocable morphological changes. The procedure carries low morbidity, and results are universally good especially if the plica is the sole pathology. Factors associated with a favourable outcome are young patient age, localised symptoms of short duration and absence of plica induced chondromalacia.

Gene signature of the embryonic meniscus.

The meniscus is a fibrocartilagenous disc in the knee that protects the joint from damage. Meniscal injuries are common, however repair efforts are largely unsuccessful and are not able to prevent the degenerative changes that result in development of osteoarthritis. Tissue regeneration in adults often recapitulates events of embryonic development, suggesting the regulatory pathways controlling morphogenesis are candidate repair signals. Here we use laser capture microdissection to collect mouse embryonic day 16 (E16) meniscus, articular cartilage, and cruciate ligaments. RNA isolated from these tissues was then used to perform genome-wide microarray analysis. We found 38 genes were differentially expressed between E16 meniscus and articular cartilage and 43 genes were differentially expressed between E16 meniscus and cruciate ligaments. Included in our data set were extracellular matrix proteins, transcription factors, and growth factors, including TGF-ß modulators (Lox, Dpt) and IGF-1 pathway members (Igf-1, Igfbp2, Igfbp3, Igfbp5). Ingenuity Pathway Analysis revealed that IGF-1 signaling was enriched in the meniscus compared to the other joint structures, while qPCR showed that Igf-1, Igfbp2, and Igfbp3 expression declined with age. We also found that several meniscus-enriched genes were expressed either in the inner or outer meniscus, establishing that regionalization of the meniscus occurs early in development.

Molecular profiling of synovial joints: use of microarray analysis to identify factors that direct the development of the knee and elbow.

BACKGROUND: Synovial joints develop from the interzone, a dense layer of mesenchymal progenitor cells that marks the site of the future joint. During the morphogenic events that follow, joints attain their distinct shape and organization. The molecular mechanisms controlling the initial specification of synovial joints has been studied, but the question of how individual joints attain the specific structure required for their unique functions remains largely unresolved. Here, we use microarray analysis to compare knee and elbow formation to identify factors involved in the development of specific joints. RESULTS: The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor-beta/bone morphogenetic protein (TGFß/BMP) and Wnt signaling. Consistent with these findings, we show that TGFß signaling directs knee morphogenesis, and is necessary for meniscus development. The tissue surrounding the elbow is highly enriched for genes involved in muscle specification and differentiation, and in splotch-delayed muscleless mutants, elbow, but not knee morphogenesis is disrupted. CONCLUSIONS: Our results suggest there are fundamental differences in how individual joints develop after interzone formation. Our microarray analyses provides a new resource for further investigation of the pathways involved in the morphogenesis of specific synovial joints.

Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.

Podoplanin is expressed by a sub-population of human foetal rib and knee joint rudiment chondrocytes.

The aim of this study was to determine if podoplanin was expressed by rudiment chondrocytes in human foetal cartilages. Podoplanin was immunolocalised in first trimester human foetal rib and knee joint rudiments to a sub-population of chondrocytes deep in the rib rudiments, tibial and femoral growth plates and cells associated with the cartilage canals of the foetal knee joint rudiments. Lymphatic vessels in the loose stromal tissues surrounding the developing rudiments were also demonstrated on the same histology slides using antipodoplanin (MAb D2-40) and anti-LYVE-1 and differentiated from CD-31 positive blood vessels confirming the discriminative capability of the antibody preparations used. The D2-40 positive rib and knee rudiment chondrocytes were not stained with antibodies to LYVE-1, CD-31 or CD-34 however perlecan was a prominent pericellular proteoglycan around these cells confirming their chondrogenic phenotype. Discernable differences were evident between the surface and deep rudiment chondrocytes in terms of their antigen reactivities detected with MAb D2-40 or antiperlecan antibodies. Binding of the cytoplasmic tail of PDPN to the ERM proteins ezrin, radixin and moeisin may result in changes in cytoskeletal organisation which alter the phenotype of this central population of rudiment cells. This may contribute to morphological changes in the rudiment cartilages which lead to establishment of the primary ossification centres and is consistent with their roles as transient developmental scaffolds during tissue development.

The morphological features of the mediopatellar and lateral folds of the developing knee joint: a fetus cadaveric study.

OBJECTIVES: The aim of the study was to evaluate the morphological features of the mediopatellar and lateral folds in fetal knees in the absence of any exposure to certain stress factors such as exercise or trauma. METHODS: The study was performed in the knee joints of 15 fetuses (6 males, 9 females) obtained as spontaneous abortion material at 20-34 weeks of gestation. The mediopatellar and lateral folds of the fetuses were classified into eight subgroups according to the following morphological features: A- Absence of folds; B- Short vertical band; C- Long vertical band; D- Narrow horizontal band; E- Broad horizontal band; F- Horizontal band accompanied by a vertical band; G- Horizontal band without a vertical band; H- Fenestrated band. RESULTS: The synovial membrane, covering the infrapatellar fat pad and forming the alar folds, extended upwards and formed the medial and lateral horizontal folds that covered the inferior part of the posterior aspect of the patella. These horizontal folds were thicker in the lower parts (close to their insertions) and became thinner towards the free ends. The horizontal band of the mediopatellar fold was observed in all cases, with an accompanying vertical band in 76.7% of the cases. A horizontally located lateral fold was absent in both knees of one fetus. The frequency of a horizontally located lateral fold was 93.3% and a vertical fold was accompanying in only 28.6% of these cases. It is of note that the horizontal band of the mediopatellar fold observed in all specimens has never been defined in previous classifications. In 10% of the knees, the vertically located part of the mediopatellar fold presented as a large band extending upward and being squeezed between the articular surface of the patella and the medial condyle of the femur. The lateral fold was observed as a large band in 10% of the knees. Another observation was that the higher level the vertical band of the mediopatellar and lateral folds began, the wider the horizontal band was, occupying more place in the patellofemoral space. It was remarkable that the frequencies of the vertically located parts of the lateral and mediopatellar folds in fetuses were higher than those reported for the adults in the literature. CONCLUSION: Our findings suggest that the resorption process of the mesenchymal tissue, particularly in the lateral part, continues until adulthood and causes age-dependent alterations in the formation of intra-articular folds. The synovial folds occupy more space between the patella and femur in the early stages of life than seen in adults. This may be a more frequent cause of unexplained knee pain in children than expected.

Hox11 genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements.

Hox11 genes are essential for zeugopod skeletal element development but their roles in synovial joint formation remain largely unknown. Here, we show that the elbow and knee joints of mouse embryos lacking all Hox11 paralogous genes are specifically remodeled and reorganized. The proximal ends of developing mutant ulna and radius elements became morphologically similar and formed an anatomically distinct elbow joint. The mutant ulna lacked the olecranon that normally attaches to the triceps brachii muscle tendon and connects the humerus to the ulna. In its place, an ulnar patella-like element developed that expressed lubricin on its ventral side facing the joint and was connected to the triceps muscle tendon. In mutant knees, both tibia and fibula fully articulated with an enlarged femoral epiphyseal end that accommodated both elements, and the neo-tripartite knee joint was enclosed in a single synovial cavity and displayed an additional anterior ligament. The mutant joints also exhibited a different organization of the superficial zone of articular cartilage that normally exerts an anti-friction function. In conclusion, Hox11 genes co-regulate and coordinate the development of zeugopod skeletal elements and adjacent elbow and knee joints, and dictate joint identity, morphogenesis and anatomical and functional organization. Notably, the ulnar patella and tripartite knee joints in the mouse mutants actually characterize several lower vertebrates, including certain reptiles and amphibians. The re-emergence of such anatomical structures suggests that their genetic blueprint is still present in the mouse genome but is normally modified to the needs of the mammalian joint-formation program by distinct Hox11 function.

Sox9-expressing precursors are the cellular origin of the cruciate ligament of the knee joint and the limb tendons.

Sox9 expression defines cell progenitors in a variety of tissues during mouse embryogenesis. To establish a genetic tool for cell-lineage tracing and gene-function analysis, we generated mice in which the CreERT2 gene was targeted to the endogenous mouse Sox9 locus. In Sox9(CreERT2/+) ;R26R embryos, tamoxifen activated Cre recombinase exclusively in Sox9-expressing tissues. To determine the suitability of this mouse line for developmental stage-specific gene recombination, we investigated the cellular origins of the cruciate ligaments of the knee joint and the limb tendons, in which precursor cells have not been defined. The cells in these tissues were labeled after tamoxifen treatment before or at the stage of chondrogenic mesenchymal condensation, indicating that ligament and tendon cells originated from Sox9-expressing cells and that cell fate determination occurred at mesenchymal condensation. This mouse line is a valuable tool for the temporal genetic tracing of the progeny of, and inducible gene modification in Sox9-expressing cells.

Morphology of the medial meniscus of the knee in human fetuses.

OBJECTIVES: The objectives were to study the morphology of the medial menisci in human fetal knee joints and to verify the developmental etiology of the discoid meniscus. MATERIAL AND METHODS: The study was carried out on 106 fetal knee joints and the morphological variants of the shapes of the medial menisci were macroscopically noted and classified. RESULTS: From our observations, 46.2% of the medial menisci were crescentic shaped, 23.6% were sided V-shaped, 13.2% had sided U-shape, 9.4% of them were sickle shaped, and 7.5% were C-shaped. In 54.71% of the cases, the medial meniscus shape was different on either side knees of the fetuses. No discoid medial menisci were seen. CONCLUSIONS: The majority of the knees were having crescentic or semi lunar shaped medial menisci and the shape of the medial meniscus was different on right and left side knee joint of the fetuses in more than fifty percent of the cases. The observations favor Kaplan's theory, as there were no discoid medial menisci observed from the fetuses of various gestational ages. Even the youngest fetus (CRL 88 mm, 14 weeks of gestation) exhibited the medial tibial plateau incompletely covered by the menisci, which did not exhibit the discoid shape. The discoid meniscus must be an abnormal finding and is due to abnormal morphogenesis.