Musculoskeletal System - Joint Development

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Developing distal phalangeal joint

In the adult, the region where two skeletal bones meet and articulate is called a "joint", that are classified based upon their: anatomical structure, mobility and shape.

In the embryo, the majority of the vertebrate skeleton is initially formed as a cartilage template, that is later replaced by bone except at the interface between two adjacent bones, leaving in the adult a layer of cartilage in this region. The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution.

Joint Links: joint | temporomandibular joint | musculoskeletal | cartilage | Category:Joint
Historic Embryology  
1940 Synovial Joints | 1952 Mandibular Joint

Musculoskeletal Links: Introduction | mesoderm | somitogenesis | limb | cartilage | bone | bone timeline | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Musculoskeletal Embryology  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee

Some Recent Findings

  • Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement[1] "Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced β-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate."
  • Development of the human shoulder joint during the embryonic and early fetal stages[2] "In our study, serial sections of 32 human embryos (Carnegie stages 16-23) and 26 fetuses (9-13 weeks) were analyzed. The chondrogenic anlagen of the humerus and the medial border of the scapula can be observed from as early as Carnegie stage 17, whereas that of the rest of the scapula appears at stage 18. The osteogenic process begins in week 10 for the humeral head and week 11 for the scapula. At stage 19 the interzone becomes apparent, which will form the glenohumeral joint. In the next stage the glenohumeral joint will begin delaminating and exhibiting a looser central band. Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum, which can be fully appreciated by stage 22. In 24-mm embryos (stage 21) we can observe, for the first time, the long head of the biceps tendon (which is already inserted in the glenoid labrum by week 9), and the intertubercular sulcus, whose depth is apparent since week 12. Regarding ligamentous structures, the coracohumeral ligament is observed at the end of Carnegie stage 23, whereas the primitive glenohumeral ligament already appeared in week 10." shoulder | limb
  • Mechanobiological simulations of prenatal joint morphogenesis[3] "Joint morphogenesis is the process in which prenatal joints acquire their reciprocal and interlocking shapes. Despite the clinical importance of the process, it remains unclear how joints acquire their shapes. In this study, we simulate 3D mechanobiological joint morphogenesis for which the effects of a range of movements (or lack of movement) and different initial joint shapes are explored. We propose that static hydrostatic compression inhibits cartilage growth while dynamic hydrostatic compression promotes cartilage growth." cartilage
  • The development of synovial joints.[4] "The position of future joints is first delimited by areas of higher cell density called interzones initially through an as yet unidentified inductive signal, subsequently specification of these regions is controlled hierarchically by WNT14 and gdf5, respectively. Joint-forming cell fate although specified is not fixed, and joints will fuse if growth factor signaling is perturbed."
  • Transcription factor ERG and joint and articular cartilage formation[5] "ets transcription factor ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of joint master regulator protein GDF-5"
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Joint Development

Lili Wang, Xiaofeng Zhang, Yingying Niu, Adel Fahmi Ahmed, Jinmei Wang, Wenyi Kang Anticoagulant activity of two novel polysaccharides from flowers of Apocynum venetum L. Int. J. Biol. Macromol.: 2018; PubMed 30521914

Zhuo Wang, Ming Yan, Jia'an Li, Jiafu Long, Yan Li, Hongmin Zhang Dual functions of STAT3 in LPS-induced angiogenesis of hepatocellular carcinoma. Biochim Biophys Acta Mol Cell Res: 2018; PubMed 30521872

Ryo Hisada, Masaru Kato, Naoki Ohnishi, Eri Sugawara, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi Antiphospholipid score is a novel risk factor for idiopathic osteonecrosis of the femoral head in patients with systemic lupus erythematosus. Rheumatology (Oxford): 2018; PubMed 30521019

Junji Zhang, Xianzhi Chai, Xiao-Peng He, Hae-Jo Kim, Juyoung Yoon, He Tian Fluorogenic probes for disease-relevant enzymes. Chem Soc Rev: 2018; PubMed 30520895

Xiao-Tan Zhang, Guang Wang, Yan Li, Manli Chuai, Kenneth Ka Ho Lee, Xuesong Yang Role of FGF signalling in neural crest cell migration during early chick embryo development. Zygote: 2018;1-8 PubMed 30520400

Joint Types

Joint development 02.jpg


  • Fibrous (synarthrodial) - immoveable joints found in cranial vault and teeth
  • Cartilagenous (synchondroses and sympheses) - partially moveable joints
  • Synovial (diarthrosis) - freely moveable joints are the most common found in the skeleton


Mouse neck joint articular cartilage. Cartilage Histology
  • Hinge - (elbow and knee) Flexion/Extension
  • Pivot - (neck, atlas and axis bones) Rotation of one bone around another
  • Ball and Socket - (shoulder and hip)
  • Saddle - (thumb)
  • Condyloid - (wrist joints)
  • Gliding - (intercarpal joints) Gliding movements

Synovial Joint Development

Skeletal joint cavity development (cavitation) occurs along planes of the future articular surfaces of synovial joints. A number of different markers have been shown to be present in the interzone at the time of cavitation (hyaluronan and hyaluronan synthase, but not chondroitin sulphates).

Fibroblast-like cells (and/or adjacent chondrocytes) with uridine-diphospho glucose dehydrogenase (UDPGD) activity contribute to glycosaminoglycan levels (increases in hyaluronan). These cells are located on the intimal surface of the synovial lining and have been suggested as the possible cavitation mechanism, switching from cellular cohesion to dissociation.[6]

Synovial Joint


This timeline data comes from a recent study of 32 human embryos (Carnegie stages 16-23) and 26 fetuses (9-13 weeks.[2]

Shoulder Development Timeline
Carnegie Stage Event
17 chondrogenic progenitor of the humerus and the medial border of the scapula can be observed.
18 chondrogenic progenitor for rest of the scapula appears.
19 glenohumeral joint will begin delaminating and showing a looser central band (interzone). Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum (glenoid ligament).
21 long head of the biceps tendon present
22 glenoid labrum (glenoid ligament) present
23 coracohumeral ligament present
Fetal Week 10 osteogenic process begins in the humeral head. Primitive glenohumeral ligament present
Fetal Week 11 osteogenic process begins in the scapula
Links: shoulder | joint | limb | timeline     Data from human histological study.[2]


In human embryo at week 7 the femur and tibia cartilage template is present (stage 18), by week 8 the posterior cruciate ligament appears (stage 21), and by stage 23 the knee cavity and the anterior cruciate ligament are both also present.[7]

Joint Morphogenesis cartoon.jpg Knee Morphogenesis
  • a - The first sign of a presumptive joint is a condensation of Col2+ limb bud progenitors at the presumptive joint site.
  • b - Joint specification is marked by induction of Gdf5 in the interzone and downregulation of Col2a1.
  • c - A joint space is formed by cavitation after progenitors for a variety of secondary joint structures are specified from the Gdf5+ progenitor pool.
  • d - Maturation of the synovial joint of the knee occurs during development and early postnatal life.

Adult Knee

  • e - Schematic representation of a healthy human knee.
  • f - Joint health in adult life is affected by genetics and environmental factors such as nutrition and exercise. Loss of joint homeostasis can trigger degenerative joint diseases such as osteoarthritis, which is characterized by degradation of articular and meniscal cartilage, formation of bone spurs and pain.

Figure from recent BMP review.[8]

Joint Abnormalities

FGFR-Related Craniosynostosis Syndromes

Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans (AN), and Muenke syndrome

Links: GeneReviews - FGFR-Related Craniosynostosis Syndromes)

Links: skull

Multiple Epiphyseal Dysplasia

Links: GeneReviews - Multiple Epiphyseal Dysplasia)


Arthrogryposis (arthrogryposis multiplex congenital, AMC) is a congenital joint contracture occurring in two or more body regions.

Large range of causes including:

  • single-gene disorders autosomal recessive, autosomal dominant or X-linked traits.
  • part of chromosomal disorders (Trisomy 18, many microdeletions and micro duplications)
  • connective tissue disorders

Temporomandibular Disorders

Links: temporomandibular joint


Clutton's joints

Historic clinical term for a symmetrical joint swelling occurring in patients of both sexes between 5 to 20 years of age with congenital syphilis. Joint swelling is usually in the knees, but can also affect the ankles, elbows, wrists and fingers. Named after Henry Hugh Clutton who first described the condition in 1886.

Links: syphilis)


  1. Singh PNP, Shea CA, Sonker SK, Rolfe RA, Ray A, Kumar S, Gupta P, Murphy P & Bandyopadhyay A. (2018). Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement. Development , 145, . PMID: 29467244 DOI.
  2. 2.0 2.1 2.2 Hita-Contreras F, Sánchez-Montesinos I, Martínez-Amat A, Cruz-Díaz D, Barranco RJ & Roda O. (2018). Development of the human shoulder joint during the embryonic and early fetal stages: anatomical considerations for clinical practice. J. Anat. , 232, 422-430. PMID: 29193070 DOI.
  3. Giorgi M, Carriero A, Shefelbine SJ & Nowlan NC. (2014). Mechanobiological simulations of prenatal joint morphogenesis. J Biomech , 47, 989-95. PMID: 24529755 DOI.
  4. Khan IM, Redman SN, Williams R, Dowthwaite GP, Oldfield SF & Archer CW. (2007). The development of synovial joints. Curr. Top. Dev. Biol. , 79, 1-36. PMID: 17498545 DOI.
  5. Iwamoto M, Tamamura Y, Koyama E, Komori T, Takeshita N, Williams JA, Nakamura T, Enomoto-Iwamoto M & Pacifici M. (2007). Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev. Biol. , 305, 40-51. PMID: 17336282 DOI.
  6. Edwards JC, Wilkinson LS, Jones HM, Soothill P, Henderson KJ, Worrall JG & Pitsillides AA. (1994). The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion. J. Anat. , 185 ( Pt 2), 355-67. PMID: 7525525
  7. Mérida-Velasco JA, Sánchez-Montesinos I, Espín-Ferra J, Mérida-Velasco JR, Rodríguez-Vázquez JF & Jiménez-Collado J. (1997). Development of the human knee joint ligaments. Anat. Rec. , 248, 259-68. PMID: 9185992
  8. Salazar VS, Gamer LW & Rosen V. (2016). BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol , 12, 203-21. PMID: 26893264 DOI.

Online Textbooks

Developmental Biology Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc. ; c2000 Forming the joints



Rountree RB, Schoor M, Chen H, Marks ME, Harley V, Mishina Y & Kingsley DM. (2004). BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biol. , 2, e355. PMID: 15492776 DOI.

Mérida-Velasco JA, Sánchez-Montesinos I, Espín-Ferra J, Mérida-Velasco JR, Rodríguez-Vázquez JF & Jiménez-Collado J. (2000). Development of the human elbow joint. Anat. Rec. , 258, 166-75. PMID: 10645964

Koyama E, Leatherman JL, Shimazu A, Nah HD & Pacifici M. (1995). Syndecan-3, tenascin-C, and the development of cartilaginous skeletal elements and joints in chick limbs. Dev. Dyn. , 203, 152-62. PMID: 7544653 DOI.

Edwards JC, Wilkinson LS, Jones HM, Soothill P, Henderson KJ, Worrall JG & Pitsillides AA. (1994). The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion. J. Anat. , 185 ( Pt 2), 355-67. PMID: 7525525

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Search July 2010 "Joint Development" All (19900) Review (3137) Free Full Text (3325)

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