Background
Methods
Protocol
Literature search strategy
Inclusion and exclusion criteria
Study selection
Data extraction
Quality assessment
Results
Identification of relevant studies
In vivo studies showed potential effects of PTH (1–34) on OA models
Author (year, country) | Subjects | Intervention | Dose (duration) | Route | Findings |
---|---|---|---|---|---|
Shao et al. (2020, China) [18] | CIOA mouse | PTH (1–34) | 10/40 μg/kg (6 weeks) | SC | PTH (1–34) exhibits protective effects on both cartilage and SCB in a dose-dependent manner via the JAK2/STAT3 signaling pathway |
Shao et al. (2021, China) [19] | CIOA mouse | PTH (1–34) | 40 μg/kg (6 weeks) | SC | PTH (1–34) exhibits protective effects on both cartilage and SCB by down-regulating the expression of JAK2/STAT3 and WNT5A/ROR2 |
Chen et al. (2021, China) [20] | Guinea pig | PTH (1–34) | 10 nM (12 weeks) | IA | PTH (1–34) improves spontaneous OA by directly affecting the cartilage rather than the SCB or metaphyseal bone |
Chen et al. (2018, China) [21] | ACLT Rats | PTH (1–34) | 10 nM (5 weeks) | IA | PTH (1–34) alleviates OA progression after ACLT and histological molecular changes by reducing chondrocyte terminal differentiation and apoptosis and by increasing autophagy |
Eswaramoorthy et al. (2012, China) [22] | PIOA Rat | PTH (1–34) | 0.4 mg (5 weeks) | IA | PTH (1–34) has beneficial effects on suppressing early OA progress PLGA microsphere-encapsulated PTH (1–34) with a controlled-release property represents a potent method to treat early OA |
Ma et al. (2017, China) [23] | SD rats | PTH (1–34) | 15 μg/kg (2/6 weeks) | SC | PTH (1–34) up-regulates the Wnt/β-catenin signaling pathway and down-regulated RUNX2 through an alternative pathway |
Zhang et al. (2022, China) [24] | Patellar ligament shortening SD rats | PTH (1–34) | 30 μg/kg (10 weeks) | SC | PTH (1–34) could improve cartilage metabolism and SCB health in early PFJOA model |
Chang et al. (2009, China) [25] | CIOA Rats | PTH (1–34) | 10 nM (10 days) | SC | PTH (1–34) treats early OA without affecting normal chondrocytes, which might a potential effectiveness of the agent for OA treatment |
Yan et al. (2014, China) [26] | Guinea pigs | PTH (1–34) | 15 μg/kg (3/6 months) | SC | PTH (1–34) prevents cartilage damage progression and retard the deterioration of SCB |
Dai et al. (2016, China) [27] | Guinea pigs | PTH (1–34) | 24 μg/kg (12 weeks) | SC | Both celecoxib and PTH (1–34) exhibit protective effects on cartilage degeneration in menisc-ectomized guinea pigs PTH (1–34) exhibits superior performance to celecoxib not only in metabolism of cartilage tissue but also in maintenance of SCB micro-architecture |
Cui et al. (2019, China) [28] | C57BL/6 J | PTH (1–34) | 40 μg/kg (4 weeks) | SC | PTH (1–34) reduces the accumulation of senescent cells in SCB by inhibiting p16 and improves bone marrow microenvironment to active bone remodeling process, indicating a potential preventative and therapeutic treatment for age-related OA |
He et al. (2021, China) [29] | DMM OA mice | PTH (1–34) | 80 μg/kg (4 weeks) | SC | PTH (1–34) has an obvious analgesic and anti-inflammatory effect, inhibits the matrix synthesis, and alleviates the OA progression PTH (1–34) inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression via the PKA pathway and the NF-κB signaling pathways |
Longo et al. (2020, China) [30] | Meniscectomy Dogs | PTH (1–34) | 2.4 μg/kg (3 weeks) | IA | PTH (1–34) promotes the regenerative and chondroprotective effects of the tissue-engineered meniscus total implantation in a canine model by inhibiting the terminal differentiation of BMSC chondrogenesis and degeneration of knee joint cartilage |
Orth et al. (2014, Germany) [31] | Rabbits | PTH (1–34) | 10 mg/kg (6 weeks) | SC | PTH (1–34) causes broadening of the calcified cartilage layer and resulting in osteoarthritic cartilage degeneration PTH (1–34)-induced alterations of the normal SCB microarchitecture may provoke early OA |
Orth et al. (2013, Germany) [32] | Rabbits osteochondral defects | PTH (1–34) | 10 μg/kg (6 weeks) | SC | PTH (1–34) stimulates articular cartilage and SCB repair, which emerges as a promising agent in the treatment of focal osteochondral defects |
Dutra et al. (2017, USA) [33] | C57BL/6 J | PTH (1–34) | 80 μg/kg (21 days) | SC | PTH (1–34) results in early mineralization of the MCC and cartilage degeneration PTH (1–34) induces alteration in the microarchitecture of the MCC and the SCB |
Sampson et al. (2011, USA) [34] | MLI OA mice | PTH (1–34) | 40 μg/kg (8 weeks) | SC | PTH (1–34) may be useful for decelerating cartilage degeneration and inducing matrix regeneration in OA model |
O'Brien et al. (2017, USA) [35] | Transgenic mice | PTH (1–34) | 80 μg/kg (2 weeks) | SC | PTH (1–34) increases the number of Col1a1/Col2a1/Col10a1-positive cells; bone volume fraction, tissue density and trabecular thickness of the SCB; proteoglycan distribution with a concomitant increase in MCC mineralization; chondrocytes differentiation and increases mineralization |
Bagi et al. (2015, USA) [36] | Posttraumatic OA Rats | PTH (1–34) | 40 μg/kg (10 weeks) | SC | A single drug will have the capacity to reduce joint inflammation, curb excessive bone remodeling, improve cartilage regeneration, and reduce pain Both Zol and PTH does not prevent or correct the deterioration of the hyaline cartilage, thickening of the SCB plate, osteophyte formation, and mechanical incapacity of the OA |
Antunes et al. (2013, USA) [37] | Prg4 mutant mice | PTH (1–34) | 50 μg/kg (6 weeks) | SC | SCB contributes to the disruption of the articular cartilage in Prg4 mutant mice PTH (1–34) could not demonstrate a protective effect in the arthropathic joints because of Prg4 mutant |
Lugo et al. (2012, Spain) [38] | OVX and ACLT rabbits | PTH (1–34) | 10 mg/kg (10 weeks) | SC | PTH (1–34) ameliorates OA by improving SCB integrity, inhibiting cartilage degradation, and exerting certain beneficial effects on synovial changes PTH (1–34) exhibits direct beneficial effects upon the synovium of this experimental model PTH (1–34) administration might hold a potential as therapeutic option for synoviopathy associated with OA |
Bellido et al. (2011, Spain) [39] | OVX and ACLT rabbits | PTH (1–34) | 10 μg/kg (10 weeks) | SC | PTH (1–34) prevents cartilage damage progression and microstructural and remodeling of SCB in rabbits with early OPOA |
In vitro studies showed potential mechanism of PTH (1–34) intracellularly
Author (year, country) | Subjects | Intervention | Dose (duration) | Route | Findings |
---|---|---|---|---|---|
Chang et al. (2009, China) [25] | Human articular chondrocytes | PTH (1–34) | 10 nM (10 days) | Co-culture | PTH (1–34) reverses the progression of terminal differentiation of human articular chondrocytes PTH (1–34) could be used to treat early OA without affecting normal chondrocytes |
Shao et al. (2022, China) [45] | BMSCs | PTH (1–34) | 10 nM (48 h) | Co-culture | PTH (1–34) alleviates OA by increasing the migration, proliferation, and chondral matrix formation of OA chondrocytes by inhibiting proinflammatory cytokines |
Chang et al. (2016, China) [46] | Human articular chondrocyte | PTHrP | 10−8 to 10−7 M (7 days) | Co-culture | PTH (1–34) is beneficial for preventing the chondro-degenerative changes initiated by dexamethasone treatment |
Mwale et al. (2010, Canada) [47] | Human MSCs | PTH (1–34) | 100 nM (48 h) | Co-culture | p38 and AKT protein kinase signaling pathways may not be required to initiate the regulation of expression of COLII and COLX by PTH (1–34), which is necessary for preventing precocious MSC hypertrophy |
Funk et al. (1998, USA) [48] | RA and OA synovial tissue | PTHrP (1–40)/PTHrP (60–72)/PTHrP (1–86) | 0.3 pM (24 h) | Co-culture | Proinflammatory cytokine-stimulated production of NH2 terminal PTHrP by synovial tissue directly invading cartilage and bone in RA, which might mediate joint destruction through direct effects on cartilage or indirectly via the induction of mediators of bone resorption |
Petersson et al. (2006, Sweden) [49] | RA or OA Chondrocytes | PTHrP (1–34) | 0.1 to 100 nM (15 days) | Co-culture | PTHrP (1–34) increases proliferation of human chondrocytes PTHrP (1–34) increases the amount of YKL-40 from chondrocytes derived from RA patients |
Music et al. (2020, Australia) [50] | BMSCs | PTH (1–34) | 0, 1, 10, or 100 nM (14 days) | Co-culture | PTH (1–34) suppresses BMSC hypertrophic gene expression in chondrogenic cultures PTH (1–34) has an anti-hypertrophic effect and a catabolic effect on BMSC as they become increasingly differentiated |
Tsukazaki et al. (1996, Japan) [51] | Human chondrocytes | PTH (l–34)/hPTHrP (l–141)/hPTHrP (100–114) | 10−13 to 10−7 M (120 min) | Co-culture | PTHrP is thought to be an important autocrine/paracrine factor for chondrocyte metabolism No significant difference of exogenously PTHrP (1–141) regard to the action of these agents, cell growth, differentiation |
Dogaki et al. (2016, Japan) [52] | Hematoma-derived progenitor cells | PTH (1–34) | 100 nM (14 days) | Co-culture | Pulsatile PTH (1–34) works on human cartilages in regarding to proliferation, osteogenic, and chondrogenic differentiation PTH (1–34) administration after fracture might positively act on other cells that contribute to fracture healing |
Hosokawa et al. (2015, Japan) [53] | ATDC5 cells | PTH (1–34) | 10−10/10−9/10−8 M (21 days) | Co-culture | PTH (1–34) regulates ATDC5 cells in both chondrogenesis and the circadian clock as time-dependent properties of chondrocyte function and differentiation |
Rutgers et al. (2019, Netherlands) [54] | Human chondrocytes | PTH (1–34) | 0.1 or 1.0 μM (4 weeks) | Co-culture | PTH (1–34) inhibits healthy human articular chondrocytes regeneration other than hypertrophic differentiation PTH (1–34) may be suitable for cartilage repair based on MSCs |