Background
Methods
Search strategies
Study selection
Author | Year | Journal | Tendon | Healthy control? | Quantitative/semiquantitative analysis and statistical tests | Investigated genes and proteins |
---|---|---|---|---|---|---|
TGF-β | ||||||
Goodier et al. [22] | 2016 |
Arthritis Res Ther
| Rotator cuff | Yes | Yes | TGFβ1, TGFβR1, TGFβR2 |
Pingel et al. [25] | 2013 |
Eur J Appl Physiol
| Achilles | Yesa
| Yes | TGFβ1 |
Pingel et al. [27] | 2012 |
BMC Musculoskeletal Disord
| Achilles | Yesa
| Yes | TGFβ1 |
de Mos et al. [28] | 2009 |
Am J Sports Med
| Achilles | Yes | Yes | TGFβ |
Fu et al. [24] | 2002 |
Clin Orthop Relat Res
| Patella | Yes | Yes | TGFβ1 |
Fenwick et al. [23] | 2001 |
J Anat
| Achilles | Yesb
| Yes | TGFβ1, TGFβ2, TGFβ3, TGβR1, TGβR2 |
BMPs | ||||||
Goodier et al. [22] | 2016 |
Arthritis Res Ther
| Rotator cuff | Yes | Yes | BMP2, BMP7 |
Rui et al. [26] | 2012 |
Knee Surg Sports Traumatol Arthrosc
| Patella | Yes | No | BMP2, BMP4, BMP7 |
Oliva et al. [29] | 2011 |
Eur Cell Mater
| Rotator cuff | Yesa
| Yes | BMP2, BMP4, BMP6 |
CTGF | ||||||
Goodier et al. [22] | 2016 |
Arthritis Res Ther
| Rotator cuff | Yes | Yes | CTGF |
Pingel et al. [27] | 2012 |
BMC Musculoskeletal Disord
| Achilles | Yesa
| Yes | CTGF |
Author | Year | Journal | Tendon | Model | Healthy control? | Quantitative/semiquantitative analysis and statistical tests | Investigated genes and proteins |
---|---|---|---|---|---|---|---|
TGF-β | |||||||
Zhang et al. [47] | 2016 |
Matrix Biol
| Achilles, mouse | Transection | Yes | Yes | TGFβ1, TGFβ2, TGFβ3, TGFβR1, TGFβR2 |
Gao et al. [30] | 2013 |
PLoS One
| FD, rat | Overuse | Yes | Yes | TGFβ1 |
Heisterbach et al. [48] | 2012 |
Knee Surg Sports Traumatol Arthrosc
| Achilles, rat | Transection → repair | Yes | Yes | TGFβ1 |
Otoshi et al. [49] | 2011 |
Arthroscopy
| Achilles, rat | Removal | Yes | Yes | TGFβ1 |
Lin et al. [50] | 2010 |
Bone
| Achilles, rat | Transection | Yes | Yes | TGFβ1, TGFβ2, TGFβ3 |
Chen et al. [51] | 2008 |
J Hand Surg Am
| FDP, chicken | Transection → repair | Yes | Yes | TGFβ |
Chan et al. [52] | 2008 |
Wound Repair Regen
| Patella, rat | Defect | Yes | Yes | TGFβ1, TGFβ2, TGFβ3, TGFβR1, TGFβR2 |
Würgler-Hauri et al. [53] | 2007 |
J Shoulder Elbow Surg
| RC, rat | Detach → repair | Yes | No | TGFβ1 |
Berglund et al. [54] | 2006 |
J Hand Surg Am
| FDP, rabbit | Division → repair | Yes | Yes | TGFβ1 |
Kobayashi et al. [55] | 2006 |
J Shoulder Elbow Surg
| RC, rabbit | Defect | Yes | No | TGFβ |
Galatz et al. [56] | 2006 |
J Orthop Res
| RC, rat | Transection → repair | Yes | Yes | TGFβ1, TGFβ3 |
Dahlgren et al. [57] | 2005 |
J Orthop Res
| FDS, horse | CI | Yes | No | TGFβ1 |
Darmani et al. [58] | 2004 |
Mediators Inflamm
| FD, rat | Crush injury | Yes | No | TGFβ |
Ngo et al. [59] | 2001 |
Plast Reconstr Surg
| FDP, rabbit | Transection → repair | Yes | No | TGFβR1, TGFβR2, TGFβR3 |
Chang et al. [60] | 1997 |
Plast Reconstr Surg
| FDP, rabbit | Transection → repair | Yes | Yes | TGFβ1 |
Natsu-ume et al. [61] | 1997 |
J Orthop Res
| Patella, rat | Transection | Yes | Yes | TGFβ |
BMPs | |||||||
Zhang et al. [47] | 2016 |
Matrix Biol
| Achilles, mouse | Transection | Yes | Yes | BMP1– BMP7, BMP12– BMP14, BMPR1, BMPR2 |
Heisterbach et al. [48] | 2012 |
Knee Surg Sports Traumatol Arthrosc
| Achilles, rat | Transection → repair | Yes | Yes | BMP12 |
Yee Lui et al. [62] | 2011 |
J Orthop Res
| Patella, rat | CI | Yes | Yes | BMP2, BMP4, BMP7 |
Lin et al. [50] | 2010 |
Bone
| Achilles, rat | Transection | Yes | Yes | BMP2, BMP4, BMP7 |
Lui et al. [63] | 2009 |
J Orthop Surg Res
| Patella, rat | CI/defect | Yes | Yes | BMP2 |
Eliasson et al. [64] | 2008 |
Clin Orthop Relat Res
| Achilles, rat | Transection | Yes | Yes | BMP7, BMP12, BMP13, BMP14, BMPR |
Würgler-Hauri et al. [53] | 2007 |
J Shoulder Elbow Surg
| RC, rat | Detach → repair | Yes | No | BMP12, BMP13, BMP14 |
CTGF | |||||||
Gao et al. [30] | 2013 |
PLoS One
| FD, rat | Overuse | Yes | Yes | CTGF |
Kietrys et al. [31] | 2012 |
PLoS One
| FD, rat | Overuse | Yes | Yes | CTGF |
Fedorczyk et al. [32] | 2010 |
J Orthop Res
| FD, rat | Overuse | Yes | Yes | CTGF |
Chen et al. [51] | 2008 |
J Hand Surg Am
| FDP, chicken | Transection | Yes | Yes | CTGF |
Asundi et al. [42] | 2008 |
Eur J Appl Physiol
| FDP, rabbit | Overuse | Yes | Yes | CTGF |
Würgler-Hauri et al. [53] | 2007 |
J Shoulder Elbow Surg
| RC, rat | Detach → repair | Yes | No | CTGF |
Berglund et al. [54] | 2006 |
J Hand Surg Am
| FDP, rabbit | Division → repair | Yes | Yes | CTGF |
Nakama et al. [43] | 2006 |
J Orthop Res
| FDP, rabbit | Overuse | Yes | Yes | CTGF |
Author | Year | Journal | Tendon | Model | Healthy control? | Quantitative/semiquantitative analysis and statistical tests | Treatment |
---|---|---|---|---|---|---|---|
TGF-β | |||||||
Fu et al. [34] | 2008 |
J Orthop Res
| Patella, rat | Defect | Yes | Yes | TGFβ1 |
BMPs | |||||||
Lui and Wong [33] | 2013 |
BMC Musculoskeletal Disord
| Patella, rat | CI | Yes | Yes | BMP2 |
Study characteristics
Study methodology and assessing the risk of bias
Results
Expression of TGF-β, BMPs and CTGF in diseased human tendon tissues
Tendon | Increased, unchanged, decreased in diseased vs control | ||
---|---|---|---|
Gene | Protein | ||
Tendinopathy | |||
TGFβ | Achilles | ↑ [29] | |
TGFβ1 | RC, Achilles, patella | ||
TGFβ2 | Achilles | ↑ [23] | |
TGFβ3 | Achilles | → [23] | |
TGFβR1 | RC, Achilles | ||
TGFβR2 | RC, Achilles | ||
BMP2 | RC, patella | → [29] | ↑ [26] |
BMP4 | RC, patella | ↓ [29] | ↑ [26] |
BMP6 | RC | ↓ [29] | |
BMP7 | Patella | ↑ [26] | |
CTGF | Achilles | ||
Tear | |||
TGFβ1 | RC | → [22] | ↓ [22] |
TGFβR1 | RC | ↓ [22] | ↓ [22] |
TGFβR2 | RC | ↑ [22] | ↓ [22] |
BMP2 | RC | → [22] | |
BMP7 | RC | → [22] | |
CTGF | RC | → [22] |
Expression of TGF-β, BMPs and CTGF in animal models of tendon injury or overuse
Animal | Tendon and model | Increased, unchanged, decreased in animal models vs control | ||
---|---|---|---|---|
Gene | Protein | |||
Injury models | ||||
TGFβ | Rat | Patella, transection (partial) | ↑ (1, 3, 7, 14, 28, 56 d) [61] | |
Chicken | FDP, transection → repair | ↑ (3 d), → (9, 14, 21 d) [51] | ||
TGFβ1 | Rat | Achilles, transection | → (2, 4, 6, 8 w) [48] | |
Achilles, removal | → (2 d), ↑ (7 d), → (30, 90, 180 d) [49] | |||
Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | ||
Rabbit | FDP, division → repair | ↑ (3, 6, 12 d), → (24 d) [54] | ||
FDP, transection → repair | → (1 d), ↑ (3, 7, 14, 28, 56 d) [60] | |||
Horse | FDS, CI | ↑ (1, 2, 4 w), → (8 w), ↑ (24 w) [57] | → (1, 2 w), ↑ (4, 8 w), → (24 w) [57] | |
TGFβ2 | Rat | Achilles, transection | ↑ (3, 5, 10 w) [50] | ↑ (3, 5, 10 w) [50] |
Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | ||
TGFβ3 | Rat | Achilles, transection | ↑ (3, 5, 10 w) [50] | ↑ (3, 5, 10 w) [50] |
Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | ||
TGFβR1 | Mouse | Achilles, transection | → (1 w), ↑ (2 w), → (4 w) [47] | |
TGFβR2 | Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | |
TGFβR3 | Mouse | Achilles, transection | → (1, 2, 4 w) [47] | |
BMP1 | Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | |
BMP2 | Rat | Achilles, transection | ↑ (3, 5, 10 w) [50] | ↑ (3, 5, 10 w) [50] |
Patella, CI | ↑ (2 w), → (4, 12 w) [63] | |||
Patella, defect | → (2, 4, 12 w) [63] | ↑ (2, 4, 12 w) [63] | ||
Mouse | Achilles, transection | ↓ (1, 2, 4 w) [47] | ||
BMP3 | Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | |
BMP4 | Rat | Achilles, transection | ↑ (3, 5, 10 w) [50] | ↑ (3, 5 w), → (10 w) [50] |
Patella, CI | ↑ (2, 4, 8, 12, 16 w) [62] | |||
Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | ||
BMP5 | Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | |
BMP6 | Mouse | Achilles, transection | → (1, 2, 4 w) [47] | |
BMP7 OP-1 | Rat | Achilles, transection | ↑ (3, 5, 10 w) [50] | ↑ (3, 5, 10 w) [50] |
Achilles, transection → unload | ↑ (3, 8 d), → (14, 21 d) [64] | |||
Achilles, transection → load | → (3, 8, 14 d), ↓ (14, 21 d) [64] | |||
Patella, CI | ↑ (2, 4, 8, 12, 16 w) [62] | |||
Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | ||
BMP12 | Rat | Achilles, transection | ↑ (2 w), → (4, 6, 8 w) [48] | |
Achilles, transection → unload | ↓ (3, 8 d), → (14, 21 d) [64] | |||
Achilles, transection → load | ↓ (3, 8 d), → (14, 21 d) [64] | |||
Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | ||
BMP13 | Rat | Achilles, transection → unload | → (3, 8, 14 d), ↓ (21 d) [64] | |
Achilles, transection → load | → (3, 8, 14 d), ↓ (21 d) [64] | |||
Mouse | Achilles, transection | → (1, 2, 4 w) [47] | ||
BMP14 | Rat | Achilles, transection → unload | ↓ (3, 8, 14, 21 d) [64] | |
Achilles, transection → load | ↓ (3, 8, 14, 21 d) [64] | |||
Mouse | Achilles, transection | ↓ (1 w), ↑ (2 w), → (4 w) [47] | ||
BMPR1a | Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | |
BMPR1b | Rat | Achilles, transection → unload | ↓ (3 d), → (8 d), ↑ (14 d), ↓ (21 d) [64] | |
Achilles, transection → load | → (3, 8, 14 d), ↓ (21 d) [64] | |||
Mouse | Achilles, transection | → (1 w), ↑ (2, 4 w) [47] | ||
BMPR2 | Rat | Achilles, transection → unload | → (3 d), ↑ (8, 14 d), ↓ (21 d) [64] | |
Achilles, transection → load | → (3 d), ↑ (8, 14 d), ↓ (21 d) [64] | |||
Mouse | Achilles, transection | ↑ (1, 2, 4 w) [47] | ||
CTGF | Rabbit | FDP, division → repair | → (3, 6, 12, 24 d) [54] | |
Chicken | FDP, transection → repair | ↑ (3 d), → (9 d), ↓ (14, 21 d) [51] | ||
Overuse models | ||||
TGFβ1 | Rat | FD, hand-pulling task | → (18 w), ↑ (24 w) [30] | |
CTGF | Rat | RC, hand-pulling task | ↑ (12 w) [31] | |
FD, hand-pulling task | ↑ (18, 24 w) [30] | |||
→ (3, 6 w), ↑ (12 w) [32] | ||||
Rabbit | FDP, electrical stimulation | →[42] | ↑[43] |
Response of tendon cells to treatment by TGF-β, BMPs or CTGF
Increased, unchanged, decreased in diseased vs control | |||
---|---|---|---|
Treatment | Cells | Gene | Protein |
TGFβ1 | Patella, rat, defect | Col1a1→, Col3a1↑, Dcn↑, Bgn → (day 7 healing) [34] Col1a1→, Col3a1→, Dcn↑, Bgn↓ (day 14 healing) [34] | |
BMP2 | Patella, rat, CI | p-Smad1/5/8↑ [33] |