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Table 3 Cellular/molecular effects of relaxin-relevant literature findings

From: Menstrual hormone-induced cyclic thumb CMC instability and degeneration in women: a systematic review

Subcategory Author, Year Findings
Basic Properties of Relaxin Goldsmith et al. 1995 [20]
Grossman et al. 2010 [32]
Lubahn et al. 2006 [4]
MacLennan et al. 1983 [13]
Powell et al. 2015 [14]
Wolf et al. 2012 [11]
Wolf et al. 2013 [15]
Relaxin (RLX*) is a peptide hormone in the insulin-like growth factor (IGF) family
Men and women have similar serum levels (400–500 pg/mL and 360–495 pg/mL), with luteal phase peaks in women
Oral contraceptives decrease relaxin below a detectable serum level
The major gene for relaxin in humans is H2; H2 relaxin binds relaxin family peptide receptor 1 and 2
The corpus luteum produces most relaxin, but synthesis occurs in the endometrium, placenta, breast tissue, and prostate
Relaxin is biologically and immunologically active during pregnancy
The capacity of relaxin to act locally means that serum levels do not always reflect activity
Properties of Relaxin Receptors Bryant-Greenwood et al. 1982 [25]
Dragoo et al. 2003 [11]
Kapila et al. 1998 [18]
Kleine et al. 2017 [33]
MacLennan et al. 1983 [13]
Powell et al. 2015 [14]
In humans, relaxin family peptide receptor-1 (RXFP) is most common, and has the highest affinity for H2 relaxin
Relaxin binds receptors in a time-, temperature-, and pH-dependent manner
RXFP expression is primed by estrogen/progesterone in chondroblasts, fibrochondroblasts, myofibroblasts, and ligaments
Estrogen-primed receptors can show maximum response at RLX* levels 10–100 times lower than normal
Estrogen, progesterone, and relaxin receptors modulate MMP§ transcription and post-translational modification
Radioreceptor location detection is a sensitive indicator of the physiological roles of RLX*
Relaxin receptors are detectable in anterior cruciate ligament (ACL) remnants of female, but not male, surgical patients
RLX* binding was uniform, saturable, and specific to the synovial lining, stromal fibroblasts, and intima
Relaxin receptors have been detected in the carpometacarpal joint of the thumb (1st CMC#) in arthroplasty patients
The synovial lining, dorsoradial ligament, volar oblique ligament, and articular cartilage cells had receptors
Concentration of RLX* receptors was significantly higher in women compared to men
Relaxin receptors have been detected in the temporomandibular joint (TMJ**), on fibrochondrocytes and ligaments
Functional, Physiologic Properties of Relaxin Ando et al. 1960 [34]
Dragoo et al. 2003 [5]
Galey et al. 2003 [35]
Goldsmith et al. 1995 [20]
Grossman et al. 2010 [32]
Nose-Ogura et al. 2017 [21]
Powell et al. 2015 [14]
Relaxin controls extracellular matrix (ECM††) turnover by stimulating collagen degradation, and suppressing synthesis
Relaxin upregulates MMP¥ production, specifically collagenases (MMP-1/-13) and gelatinases (MMP§-2/-9)
Active collagenases cleave tropocollagen, making it susceptible to subsequent denaturation by gelatinases
The density and organization of collagen bundles, and total local collagen content decrease
MMP§s induced by relaxin degrade collagen at a nanoscale level, and macro-level effects are not always appreciable
Relaxin has dose-dependent and differential functioning; its effects depend on location and presence of other hormones
There is a significant correlation between peak serum relaxin and peak serum progesterone levels
Intracellular relaxin activates MAPK‡‡ and PI3K§§, increasing cAMP¶¶ and triggering vasodilation via MMP§-2/-9
Estrogen, progesterone, and relaxin binding synovial receptors upregulates inflammatory MMP§s, increasing OA## risk
Relaxin upregulates production of collagenases and gelatinases in ligaments and fibrocartilage
During parturition, relaxin binding pubic ligaments dissociates collagen, increases water uptake, and decreases viscosity